1,011 results
Search Results
2. The Effects of Different Antigen–Antibody Pairs on the Results of 20 Min ELISA and 8 Min Chromatographic Paper Test for Quantitative Detection of Acetamiprid in Vegetables.
- Author
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Wu, Yuxiang, Guo, Yemin, Yang, Qingqing, Li, Falan, and Sun, Xia
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BOOSTER vaccines ,ENZYME-linked immunosorbent assay ,QUANTUM dots ,CELL fusion ,ANTIBODY formation ,VEGETABLES - Abstract
To establish rapid, high-sensitive, quantitative detection of ACP residues in vegetables. A 1G2 cell clone was selected as the most sensitive for anti-ACP antibody production following secondary immunization, cell fusion, and screening. The affinity of the 1G2 antibody to each of the four coating agents (imidacloprid–bovine serum albumin [BSA], thiacloprid–BSA, imidaclothiz–BSA, and ACP-BSA) was determined using a 20 min enzyme-linked immunosorbent assay (ELISA). The half maximal inhibitory concentration (IC
50 ) was 0.51–0.62 ng/mL, showing no significant difference in affinity to different antigens. However, we obtained IC50 values of 0.58 and 1.40 ng/mL on the linear regression lines for 1G2 anti-ACP antibody/imidacloprid–BSA and 1G2 anti-ACP antibody/thiacloprid–BSA, respectively, via quantum dot (QD)-based immunochromatography. That is, the 1G2 antibody/imidacloprid–BSA pair (the best combination) was about three times more sensitive than the 1G2 antibody/thiacloprid–BSA pair in immunochromatographic detection. The best combination was used for the development of an 8 min chromatographic paper test. With simple and convenient sample pretreatment, we achieved an average recovery of 75–117%. The coefficient of variation (CoV) was <25% for all concentrations tested, the false–positive rate was <5%, the false–negative rate was 0%, and the linear range of the method was 50–1800 μg/kg. These performance metrics met the ACP detection standards in China, the European Union (EU), and the United States (US). In summary, in this study, we established an 8 min QD-based immunochromatographic stripe for the rapid and accurate quantitative determination of ACP residues in vegetables. [ABSTRACT FROM AUTHOR]- Published
- 2022
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3. Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera.
- Author
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Roper, Kelly J., Thomas, Jordan, Albalawi, Wejdan, Maddocks, Emily, Dobson, Susan, Alshehri, Abdullateef, Barone, Francesco G., Baltazar, Murielle, Semple, Malcolm G., Ho, Antonia, Turtle, Lance, Donegan, Cara, Spencer, Rebecca G., Moore, Shona C., Hardwick, Hayley, Solomon, Tom, Turtle, Lance C. W., da Silva Filipe, Ana, Ho, Antonia Ying Wai, and McDonald, Sarah E.
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ANTIBODY formation ,SARS-CoV-2 ,DRIED blood spot testing ,RESOURCE-limited settings ,COVID-19 pandemic ,IMMUNOGLOBULINS - Abstract
The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients
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Ulf Petrausch, Michele Atzl, Hanno Ulmer, Thomas Winder, Andreas Volgger, Magdalena Benda, Peter Fraunberger, Theresia Lang, Minh Huynh, Bernd L. Hartmann, Claudia Grabher, Beatrix Mutschlechner, Klaus Gasser, Luciano Severgnini, and Patrick Reimann
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Male ,medicine.medical_specialty ,COVID-19 Vaccines ,Lymphoma ,Lymphocyte ,Antibodies, Viral ,Gastroenterology ,Immunoglobulin G ,Serology ,immune cells ,Immune system ,COVID‐19 ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Lymphocytes ,BNT162 Vaccine ,Aged ,Retrospective Studies ,Immunoassay ,BNT162b2 mRNA vaccine ,biology ,SARS-CoV-2 ,business.industry ,COVID-19 ,Hematology ,Middle Aged ,medicine.disease ,Research Papers ,Leukemia, Lymphocytic, Chronic, B-Cell ,Killer Cells, Natural ,Vaccination ,medicine.anatomical_structure ,Hematologic Neoplasms ,Predictive value of tests ,Antibody Formation ,serological response ,biology.protein ,Female ,Safety ,Antibody ,business ,chronic lymphocytic leukaemia ,Research Paper - Abstract
Summary Haemato‐oncological patients are at risk in case of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection. Currently, vaccination is the best‐evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato‐oncological patients. A total of 259 haemato‐oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti‐SARS‐CoV‐2‐S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P
- Published
- 2021
5. The challenges and breakthroughs in the development of diagnostic monoclonal antibodies.
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Wang, Jing, Song, Qitao, Yang, Tao, Li, Yuanli, Zhang, Lihua, Li, Jiayan, Liu, Feifei, Lin, Yanyin, Xu, Xiaoxia, Heng, Yu, Xu, Lulai, Zhang, Shun, Zhou, Jiahui, Liu, Yunbo, Kong, Lingyuan, Tang, Dingbin, Ji, Chengdong, Tan, Bing, Liao, Pu, and Pan, Nengke
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MONOCLONAL antibodies ,B cells ,ARTIFICIAL intelligence ,SYNTHETIC antibodies ,ANTIBODY formation ,TECHNOLOGICAL innovations ,DISPLAY systems ,MACHINE learning - Abstract
Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products. [ABSTRACT FROM AUTHOR]
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- 2024
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6. mRNA intramuscular vaccination produces a robust IgG antibody response in advanced neuromuscular disease
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Thomas W. McDade, Alexis R. Demonbreun, Amelia Sancilio, Elizabeth M. McNally, Rana Saber, Matthew P. Velez, and Daniel T. Ryan
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Male ,Serology ,Drug Interactions ,Muscular dystrophy ,Neutralizing antibody ,Genetics (clinical) ,receptor binding domain ,biology ,Neuromuscular Diseases ,Middle Aged ,Neuromuscular disease ,Research Highlight ,Vaccination ,Neurology ,dried blood spots ,Female ,Steroids ,ELISA ,mRNA Vaccines ,neuromuscular ,Antibody ,Glucocorticoid ,2019-nCoV Vaccine mRNA-1273 ,Research Paper ,medicine.drug ,Adult ,muscular dystrophy ,COVID-19 Vaccines ,IgG ,serological testing ,Young Adult ,Immune system ,Neutralization Tests ,medicine ,Humans ,BNT162 Vaccine ,Aged ,Epilepsy ,SARS-CoV-2 ,business.industry ,COVID-19 ,medicine.disease ,Immunoglobulin G ,Antibody Formation ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Neurology (clinical) ,business - Abstract
SARS-CoV-2 vaccines protect against symptomatic and severe COVID-19. The BNT162b2/Pfizer and mRNA-1273/Moderna vaccines represent new vaccine technology relying on administration of mRNA encoding SARS-CoV-2 viral spike protein encased in lipid nanoparticles. The vaccines are administered as two doses into muscle, which elicits a strong response, typically within 14 days after the second dose. Neuromuscular diseases are characterized by the progressive loss of muscle and are often treated with chronic glucocorticoid steroids, both of which may contribute to a blunted immune response to vaccination. Herein, we measured IgG antibody content and neutralizing antibody response after mRNA COVID-19 vaccination in non-ambulatory neuromuscular disease patients. After two doses of mRNA COVID-19 vaccine, median anti-receptor binding domain IgG and percent surrogate viral neutralization in non-ambulatory neuromuscular disease samples were significantly elevated similar to healthy vaccinated controls. As in healthy controls, COVID-19 vaccines produce greater antibody levels compared to those with a history of outpatient COVID-19 infection. This data documents that non-ambulatory neuromuscular disease patients respond well to two doses of mRNA COVID-19 vaccine despite low muscle mass and even chronic steroid use.
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- 2022
7. The dynamics and association of B and T cell receptor repertoires upon antibody response to hepatitis B vaccination in healthy adults
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Hongkai Wu, Anqi Zheng, Miaoxian Zhao, Zhanhui Wang, Ying Xu, Mingxing Gong, Xueying Li, Shi Xie, and Rong Yan
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Adult ,Hepatitis B vaccine ,Receptors, Antigen, T-Cell, alpha-beta ,030231 tropical medicine ,Immunology ,B-cell receptor ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Immunology and Allergy ,Hepatitis B Vaccines ,030212 general & internal medicine ,Hepatitis B Antibodies ,Pharmacology ,Hepatitis B virus ,business.industry ,Repertoire ,Vaccination ,T-cell receptor ,Hepatitis B ,medicine.disease ,Virology ,Antibody response ,Hepatitis b vaccination ,Antibody Formation ,sense organs ,business ,Research Paper - Abstract
The Hepatitis B (HB) vaccine is efficacious in preventing hepatitis B virus infection. However, the association between antibody response to the HB vaccine and dynamic immune repertoire changes in different cell subsets remains unclear. Nine healthy participants were administered three doses of HB vaccine following the 0, 1, 6 month schedule. Peripheral CD4(+) T, memory B (MB), naïve B (NB), and plasma cells (PCs) were sorted before vaccination and 7 days following each dose. The complementary determining region 3 of T-cell receptor β (TCRβ) chain and B-cell receptor (BCR) heavy chain (IgG, IgM, IgA) repertoires were analyzed by high-throughput sequencing. All nine participants elicited protective antibody titers to the vaccine at the end of immunization. Compared with the baseline, MB cells showed a significant increase in IgG usage and decreased IgM usage and repertoire diversity at the end of vaccination. TCRβ diversity changes were highly correlated with those of the BCR in MB cells in participants with a faster and robust antibody responses. The percentage of shared clonotypes between NB and MB cells, and MB cells and PCs were much higher than that between NB cells and PCs. The more clonotypes sharing the faster and stronger antibody responses were observed after HB vaccination. These results suggest the integral involvement of MB cells in vaccine immunization. Interaction between CD4(+) T and MB cells and B cell differentiation may improve antibody response to HB vaccine.
- Published
- 2021
8. The impact of physical frailty on the response to inactivated influenza vaccine in older adults
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Uma R. Chandran, Krissy K. Moehling, Mary Patricia Nowalk, Marianna A. Ortiz, Bo Zhai, John F. Alcorn, Michael Susick, Richard K. Zimmerman, David A. Nace, Min Z. Levine, Chyongchiou J. Lin, and William E. Schwarzmann
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Male ,Aging ,Influenza vaccine ,T-Lymphocytes ,frailty ,Peripheral blood mononuclear cell ,immune response ,Immune system ,Assisted Living Facilities ,Influenza, Human ,peripheral cell mediated immunity ,Humans ,Medicine ,Seroconversion ,Aged ,Cell Proliferation ,Aged, 80 and over ,Hemagglutination assay ,business.industry ,Interleukin-8 ,Antibody titer ,virus diseases ,Cell Biology ,Hemagglutination Inhibition Tests ,Middle Aged ,Vaccination ,Oxidative Stress ,Titer ,Vaccines, Inactivated ,Influenza Vaccines ,Case-Control Studies ,Antibody Formation ,Immunology ,Leukocytes, Mononuclear ,Female ,Independent Living ,Interferons ,antibody titers ,influenza ,business ,Research Paper - Abstract
Physical frailty’s impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.
- Published
- 2020
9. Optimization and qualification of an assay that demonstrates that a FimH vaccine induces functional antibody responses in women with histories of urinary tract infections
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Gary R. Eldridge, Steven M. Martin, Michelle M Miller, Courtney M. Starks, Joshua Cubbison, and Peter M Broglie
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Functional assay ,medicine.drug_class ,Urinary system ,fimH ,030231 tropical medicine ,Immunology ,Antibiotics ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,vaccine ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Pharmacology ,Urinary tract infection ,Adhesins, Escherichia coli ,Vaccines ,TLR-4 agonist ,biology ,business.industry ,Bacterial adhesin ,Antibody response ,Antibody Formation ,Urinary Tract Infections ,biology.protein ,Female ,Fimbriae Proteins ,Antibody ,business ,functional assay ,Research Article ,Research Paper - Abstract
Recurrent urinary tract infections (rUTI) are a serious disease associated with morbidities and mortality. Resistance to the standard of care antibiotics is now widespread because of the continued use of antibiotics among people who suffer from rUTI. We are therefore developing a vaccine to prevent recurrences among patients with rUTI. The antigen of the vaccine is FimH, a bacterial adhesin protein, and the vaccine is adjuvanted with a TLR-4 agonist. In a Phase 1 clinical study evaluating the vaccine, immunized individuals produced FimH-binding antibodies. Here we describe the optimization, qualification, and use of an assay to assess the functionality of these anti-FimH antibodies. The suitability of the assay for its intended purpose was demonstrated by selectivity, specificity, sensitivity, and intra-assay and inter-assay precision. The acceptance criteria were achieved for all parameters including intra-assay precision with ≤10% relative standard deviations and inter-assay precision with ≤25% relative standard deviations. The results presented herein suggest this functional assay will be important for supporting the vaccine’s efficacy in future human studies. Furthermore and of great significance, these results prove that vaccine-induced functional antibodies can be elicited in rUTI patients against an essential virulence factor, FimH.
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- 2020
10. Study of the association of seventeen single nucleotide polymorphisms and their haplotypes in the TNF-α, IL-2, IL-4 and IL-10 genes with the antibody response to inactivated Japanese encephalitis vaccine
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Jun Chen, Mingbo Sun, Li Shi, Yan Deng, Xiaona Wang, Yaheng Li, Qiongzhou Yin, Yufeng Yao, Xiuwen Xu, Huijuan Yang, Zhimei Zhao, and Shuyuan Liu
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Male ,IL-4 and IL-10 genes ,animal diseases ,viruses ,030231 tropical medicine ,Immunology ,SNP ,chemical and pharmacologic phenomena ,Single-nucleotide polymorphism ,Biology ,Antibodies, Viral ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Japanese encephalitis vaccine ,Encephalitis, Japanese ,Interleukin 4 ,Pharmacology ,Japanese Encephalitis Vaccines ,Tumor Necrosis Factor-alpha ,IL-2 ,Haplotype ,antibody response ,biochemical phenomena, metabolism, and nutrition ,Interleukin-10 ,Interleukin 10 ,Immunization ,Haplotypes ,TNF-α ,Antibody Formation ,bacteria ,Interleukin-2 ,Female ,Interleukin-4 ,inactivated Japanese encephalitis vaccine ,medicine.drug ,Research Article ,Research Paper - Abstract
To investigate whether the TNF-α, IL-2, IL-4 and IL-10 genes contribute to variations in vaccine-induced immune responses after immunization with the inactivated Japanese encephalitis vaccine (IJEV), a total of 369 individuals who received the IJEV were enrolled. Based on Japanese encephalitis virus (JEV) neutralization antibodies (NAbs), the individuals were divided into seropositive (SP) and seronegative (SN) groups. Then, 17 SNPs in the TNF-α, IL-2, IL-4 and IL-10 genes were genotyped using the TaqMan method. Although there was no association of the TNF-α, IL-2, IL-4 and IL-10 genes with JEV seropositivity triggered by JEV vaccination when all the individuals in the SP and SN groups were compared, differences were observed in a subgroup analysis. In the male group, rs2243291 in the IL-4 gene showed a difference between the JEV SP and SN groups with the overdominant model (P = .045), and the C/G genotypes conferred more JEV seropositivity (OR = 1.87; 95% CI: 1.01–3.49); the CT genotype of rs3093726 in the TNF-α gene showed higher JEV NAbs geometric mean titer (GMT) than the TT genotype (P = .018, CT: 1.677 ± 0.144 vs TT: 1.271 ± 0.039). Furthermore, the rs1800629 genotype in the TNF-α gene and the rs1800896 genotype in the IL-10 gene exhibited a trend of association with JEV seropositivity in the female group, but the difference was not significant. The present study suggested that the polymorphisms in the cytokine genes could be associated with sex-specific JEV NAbs seroconversion. However, more samples should be studied, and further functional verification should be performed.
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- 2020
11. Nutrient supplementation strategy improves cell concentration and longevity, monoclonal antibody production and lactate metabolism of Chinese hamster ovary cells
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Saumel Pérez-Rodriguez, Norma A. Valdez-Cruz, María de Jesús Ramírez-Lira, and Mauricio A. Trujillo-Roldán
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0106 biological sciences ,0301 basic medicine ,Culture mediums ,media_common.quotation_subject ,Longevity ,Bioengineering ,CHO Cells ,Biology ,01 natural sciences ,Applied Microbiology and Biotechnology ,law.invention ,03 medical and health sciences ,Cricetulus ,monoclonal antibody production ,law ,Cricetinae ,010608 biotechnology ,Nutrient supplementation ,Animals ,Lactic Acid ,Cell Proliferation ,media_common ,Monoclonal antibody production ,Chinese hamster ovary cell ,Antibodies, Monoclonal ,chinese hamster ovary cells ,cellular growth ,General Medicine ,Cell concentration ,powerfeed a ,Culture Media ,030104 developmental biology ,Biochemistry ,Lactate metabolism ,Antibody Formation ,Recombinant DNA ,metabolism ,TP248.13-248.65 ,Research Paper ,Biotechnology - Abstract
A careful selection of culture mediums and feeds has become necessary to maximize yields of recombinant proteins during bioprocesses of mammalian cells. Supplements contain a variety of concentrate nutrients, and their beneficial effects vary according to recombinant cell lines. In this study, the effects of PowerFeed A on growth kinetics, productivity and cellular metabolism were evaluated for two Chinese hamster ovary cell lines producing a monoclonal antibody in a batch culture. Supplemented cultures increased integral viable cell density of CRL-12444 and CRL-12445 cells by 2.4 and 1.6 times through extension of culture time at which viability was above 90% in 72 and 36 h, respectively, and increment of maximal cell concentration in 3.25 × 106 cells/ml (69%) for CRL-12445 cells. Product titer augmented 1.9 and 2.5 times for CRL-12444 and CRL-12445 cells, respectively, without changes in growth rate and specific productivity. Feed supplementation also stimulated full consumption of glucose and free glutamine and reduced 10 times lactate accumulation, while ammonium, sodium and potassium remained at similar concentrations at the end of the culture. About 44% of calcium, mainly provided by feed, was consumed by both cell lines. Maximization of cellular growth, viability and protein titer through feeding encourages extending its use to other cell lines and exploring novel combinations with other basal mediums or feeds. A thorough investigation of its impact on protein quality and the molecular mechanisms behind these effects will allow designing effective feeds and strategies to rationally optimize protein production in the biomanufacturing industry., Graphical Abstract
- Published
- 2020
12. ABO blood group and SARS‐CoV‐2 antibody response in a convalescent donor population
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Imani Burgess, Brenda J. Grossman, Eric A. Gehrie, Christi E. Marshall, Ruchika Goel, Oliver Laeyendecker, Kirsten Littlefield, Thomas C. Quinn, Jeffrey L. Winters, Ruchee Shrestha, Andrew D. Redd, David J. Sullivan, Evan M. Bloch, Arturo Casadevall, Shmuel Shoham, Aaron A.R. Tobian, Eshan U. Patel, and Andrew Pekosz
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Population ,Blood Donors ,030204 cardiovascular system & hematology ,Antibodies, Viral ,Group B ,SARS‐CoV‐2 ,ABO Blood-Group System ,03 medical and health sciences ,0302 clinical medicine ,COVID-19 Testing ,COVID‐19 ,ABO blood group system ,Medicine ,Microneutralization Assay ,Humans ,Neutralizing antibody ,education ,COVID-19 Serotherapy ,education.field_of_study ,Original Paper ,biology ,business.industry ,SARS-CoV-2 ,Immunization, Passive ,COVID-19 ,Hematology ,General Medicine ,titre ,Original Papers ,ABO group ,Agglutination (biology) ,Titer ,Immunology ,convalescent plasma ,Antibody Formation ,biology.protein ,Antibody ,business ,030215 immunology - Abstract
BACKGROUND AND OBJECTIVES: ABO blood group may affect risk of SARS-CoV-2 infection and/or severity of COVID-19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS-CoV-2 vary by ABO blood group. MATERIALS AND METHODS: Among eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti-SARS-CoV-2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non-parametric Kruskal-Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS-CoV-2 diagnosis. RESULTS: Of the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti-spike IgA or anti-spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1-3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4-1·0], P = 0·053). CONCLUSION: Eligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID-19 severity are needed.
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- 2021
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13. Baseline characteristics of SARS-CoV-2 vaccine non-responders in a large population-based sample.
- Author
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Yaseen, Ashraf, DeSantis, Stacia M., Sabharwal, Rachit, Talebi, Yashar, Swartz, Michael D., Zhang, Shiming, Leon Novelo, Luis, Pinzon-Gomez, Cesar L., Messiah, Sarah E., Valerio-Shewmaker, Melissa, Kohl III, Harold W., Ross, Jessica, Lakey, David, Shuford, Jennifer A., Pont, Stephen J., and Boerwinkle, Eric
- Subjects
COVID-19 vaccines ,DISEASE risk factors ,VACCINE effectiveness ,ANTIBODY formation ,COVID-19 pandemic - Abstract
Introduction: Studies indicate that individuals with chronic conditions and specific baseline characteristics may not mount a robust humoral antibody response to SARS-CoV-2 vaccines. In this paper, we used data from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a longitudinal state-wide seroprevalence program that has enrolled more than 90,000 participants, to evaluate the role of chronic diseases as the potential risk factors of non-response to SARS-CoV-2 vaccines in a large epidemiologic cohort. Methods: A participant needed to complete an online survey and a blood draw to test for SARS-CoV-2 circulating plasma antibodies at four-time points spaced at least three months apart. Chronic disease predictors of vaccine non-response are evaluated using logistic regression with non-response as the outcome and each chronic disease + age as the predictors. Results: As of April 24, 2023, 18,240 participants met the inclusion criteria; 0.58% (N = 105) of these are non-responders. Adjusting for age, our results show that participants with self-reported immunocompromised status, kidney disease, cancer, and "other" non-specified comorbidity were 15.43, 5.11, 2.59, and 3.13 times more likely to fail to mount a complete response to a vaccine, respectively. Furthermore, having two or more chronic diseases doubled the prevalence of non-response. Conclusion: Consistent with smaller targeted studies, a large epidemiologic cohort bears the same conclusion and demonstrates immunocompromised, cancer, kidney disease, and the number of diseases are associated with vaccine non-response. This study suggests that those individuals, with chronic diseases with the potential to affect their immune system response, may need increased doses or repeated doses of COVID-19 vaccines to develop a protective antibody level. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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14. Dynamic analysis and optimal control of a fractional order HIV/HTLV co-infection model with HIV-specific antibody immune response.
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Ruiqing Shi and Yihong Zhang
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PONTRYAGIN'S minimum principle ,T cells ,ANTIBODY formation ,MIXED infections ,HTLV ,IMMUNE response ,HIV - Abstract
In this paper, a fractional order HIV/HTLV co-infection model with HIV-specific antibody immune response is established. Two cases are considered: constant control and optimal control. For the constant control system, the existence and uniqueness of the positive solutions are proved, and then the sufficient conditions for the existence and stability of five equilibriums are obtained. For the second case, the Pontryagin's Maximum Principle is used to analyze the optimal control, and the formula of the optimal solution are derived. After that, some numerical simulations are performed to validate the theoretical prediction. Numerical simulations indicate that in the case of HIV/HTLV co-infection, the concentration of CD4
+ T cells is no longer suitable as an effective reference data for understanding the development process of the disease. On the contrary, the number of HIV virus particles should be used as an important indicator for reference. [ABSTRACT FROM AUTHOR]- Published
- 2024
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15. No SARS‐CoV ‐2 antibody response in 25 patients with pseudo‐chilblains
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Iris González-Villanueva, Eduardo Vergara-de Caso, Isabel Betlloch-Mas, Alexandre Docampo-Simón, Juan Carlos Palazón-Cabanes, Gloria Juan-Carpena, Adelina Gimeno-Gascon, Mar Blanes-Martínez, and María José Sánchez-Pujol
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,coronavirus ,Dermatology ,medicine.disease_cause ,Polymerase Chain Reaction ,chilblains ,SARS‐CoV‐2 ,Serology ,Short Papers ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,COVID-19 Testing ,0302 clinical medicine ,COVID‐19 ,Internal medicine ,medicine ,Short Paper ,Humans ,Outpatient clinic ,Prospective Studies ,Child ,Chilblains ,Prospective cohort study ,Coronavirus ,acral ,SARS-CoV-2 ,business.industry ,COVID-19 ,Infant ,virus diseases ,General Medicine ,Middle Aged ,medicine.disease ,Antibody response ,Child, Preschool ,030220 oncology & carcinogenesis ,Antibody Formation ,Quarantine ,Female ,business - Abstract
Chilblain‐like acral lesions have been identified in some coronavirus disease 2019 (COVID‐19) patients. It has been suggested that these pseudo‐chilblains could be a specific marker of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Most patients with these lesions have had negative polymerase chain reactions (PCRs), but some authors believe serology tests are likely to give positive results. We designed a prospective study including all patients with pseudo‐chilblains treated in outpatient department in April and May 2020 and then performed SARS‐CoV‐2 PCR and serology tests on all available patients. We evaluated 59 patients, of whom 17 had undergone PCR before the study period, all with negative results. For the present study, we performed 20 additional PCRs, serology tests in 25 patients, and a parvovirus B19 antibody test in 15 patients. All results were negative. Our findings counter the hypothesis that serology is likely to reveal SARS‐CoV‐2 infection in patients with pseudo‐chilblains. One hypothesis for our negative results is that the time period between symptom onset and antibody production is longer in these patients; another is that the lesions are caused by behavioral changes during lockdown rather than SARS‐CoV‐2 infection. We nevertheless maintain that COVID‐19 should be ruled out in people presenting with chilblain‐like lesions.
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- 2020
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16. Antibody responses after a single dose of ChAdOx1 nCoV-19 vaccine in healthcare workers previously infected with SARS-CoV-2
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Henry Ng, Mia Phillipson, Kim Blom, Ulrika Marking, Sara M. Mangsbo, Peter Nilsson, Ann-Christin Salomonsson, Sophia Hober, Sebastian Havervall, Charlotte Thålin, Max Gordon, Jonas Klingstrom, Nina Greilert-Norin, Mikael Åberg, Cecilia Hellström, and Elisa Pin
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Adult ,Male ,Infectious Medicine ,Medicine (General) ,Research paper ,COVID-19 Vaccines ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Health Personnel ,Neutralizing antibody response ,Immunization, Secondary ,Infektionsmedicin ,General Biochemistry, Genetics and Molecular Biology ,Serology ,Immune system ,R5-920 ,Prior infection ,ChAdOx1 nCoV-19 ,Blocking antibody ,Medicine ,Humans ,skin and connective tissue diseases ,BNT162 Vaccine ,BNT162b2 vaccine ,biology ,business.industry ,SARS-CoV-2 ,fungi ,Vaccination ,Wild type ,COVID-19 ,General Medicine ,Middle Aged ,Antibodies, Neutralizing ,body regions ,Regimen ,Immunoglobulin G ,Immunology ,Antibody Formation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Female ,Antibody ,business - Abstract
Background Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infection are however limited, and current guidelines recommend a two-dose regimen regardless of preexisting immunity. Methods We compared RBD-specific IgG and RBD-ACE2 blocking antibodies against SARS-CoV-2 wild type and variants of concern following two doses of the mRNA vaccine BNT162b2 in SARS-CoV-2 naive healthcare workers (n=65) and a single dose of the adenovector vaccine ChAdOx1 nCoV-19 in 82 healthcare workers more than (n=45) and less than (n=37) 11 months post mild SARS-CoV-2 infection at time of vaccination. Findings The post-vaccine levels of RBD-specific IgG and neutralizing antibodies against the SARS-CoV-2 wild type and variants of concern including Delta lineage 1.617.2 were similar or higher in participants receiving a single dose of ChAdOx1 nCoV-19 vaccine post SARS-CoV-2 infection (both more than and less than 11 months post infection) compared to SARS-CoV-2 naive participants who received two doses of BNT162b2 vaccine. Interpretation Our data support that a single dose ChAdOx1 nCoV-19 vaccine that is administered up to at least 11 months post SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen. Funding A full list of funding bodies that contributed to this study can be found in the Acknowledgements section
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- 2021
17. Position statement on the use of biosimilars in inflammatory bowel disease
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Emanuel Burri, Christian Mottet, Pierre Michetti, Michel H. Maillard, Pascal Juillerat, Stephan R. Vavricka, Nadine Zahnd, Michael Manz, Gerhard Rogler, and University of Zurich
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Position statement ,030213 general clinical medicine ,medicine.medical_specialty ,610 Medicine & health ,2700 General Medicine ,Inflammatory bowel disease ,Drug Prescriptions ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Intensive care medicine ,Biosimilar Pharmaceuticals ,Drug Approval ,Clinical Trials as Topic ,business.industry ,Drug Substitution ,Treatment options ,Biosimilar ,General Medicine ,medicine.disease ,Inflammatory Bowel Diseases ,Safety profile ,10219 Clinic for Gastroenterology and Hepatology ,030220 oncology & carcinogenesis ,Antibody Formation ,Position paper ,business ,Antibody formation - Abstract
Biologics are effective and have a good safety profile in the treatment of inflammatory bowel disease. Biosimilars have recently become available as treatment option. They are biological agents that are highly similar to the original biologic compound in their structure, biological activity, efficacy and safety. This position paper summarises current knowledge on biosimilars and presents its statements on regulatory issues and clinical situation in order to provide clinicians adequate information for them to reach informed and appropriate shared decision-making with their patients.
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- 2019
18. Development of Human Leukocyte Antigen (HLA) Antibodies Against Vascular Homograft Donor in Pediatric Heart Transplant Recipients
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Jaana Pihkala, Alireza Raissadati, Timo Jahnukainen, Jouni Lauronen, Hannu Jalanko, Juha Puntila, Tommi Pätilä, Ilkka Mattila, Elisa Ylinen, Jukka T. Salminen, HUS Children and Adolescents, Children's Hospital, University of Helsinki, Lastentautien yksikkö, Clinicum, and Lastenkirurgian yksikkö
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Graft Rejection ,Male ,IMPACT ,medicine.medical_treatment ,CHILDREN ,030204 cardiovascular system & hematology ,030230 surgery ,Gastroenterology ,0302 clinical medicine ,Isoantibodies ,HLA Antigens ,NOMENCLATURE ,Hla antibodies ,Child ,Heart transplantation ,biology ,Graft Survival ,General Medicine ,3. Good health ,HEMODIALYSIS ACCESS ,surgical procedures, operative ,medicine.anatomical_structure ,REJECTION ,Child, Preschool ,WORKING FORMULATION ,Cohort ,Female ,Antibody ,Artery ,medicine.medical_specialty ,Adolescent ,Allosensitization ,INTERNATIONAL SOCIETY ,ALLOGRAFT ,Human leukocyte antigen ,03 medical and health sciences ,Internal medicine ,Cadaver ,medicine ,Humans ,Retrospective Studies ,Original Paper ,Transplantation ,VALVES ,business.industry ,Infant ,Retrospective cohort study ,3126 Surgery, anesthesiology, intensive care, radiology ,body regions ,Antibody Formation ,biology.protein ,Heart Transplantation ,Vascular Grafting ,IMPLANTATION ,business - Abstract
Background: The appearance of human leukocyte antigen (HLA) antibodies after solid organ transplantation predisposes recipients to graft dysfunction. In theory, vascular homografts, which are widely used in children with congenital heart defects, may cause allosensitization. Material/Methods: In this single-center retrospective study, the presence of pre-existing HLA antibodies in pediatric heart trans- plant (HTx) recipients with a vascular homograft was evaluated in a cohort of 12 patients. HLA antibodies were screened before and after HTx and positive screening results were confirmed and identified using the Luminex (R) single antigen bead method. Endomyocardial biopsies (EMB) and coronary angiography studies were re-evaluated to assess the prevalence of acute rejections and coronary artery change in these patients. Results: At the time of HTx, 8 patients (67%) had HLA antibodies detected by the Luminex assay, none of which were heart donor specific (DSA). All patients had negative leukocyte crossmatch. One patient developed DSAs against homograft donor prior to HTx. After the HTx, 5 patients (42%) developed DSAs against the heart donor and 4 patients (40%) against the homograft donor. In 2 patients (17%), the antibodies were against both heart and homograft donors. The rejection rate or prevalence of coronary artery vasculopathy did not differ significantly between the homograft cohort and our historical controls. Conclusions: Our results suggest that the prevalence of DSAs against homograft donor prior to HTx is relatively rare. However, almost half of the patients developed DSAs against homograft post-HTx. The clinical importance of these antibodies warrants further studies.
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- 2019
19. Template Theories, the Rule of Parsimony, and Disregard for Irreproducibility--The Example of Linus Pauling's Research on Antibody Formation.
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DEICHMANN, UTE
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ANTIBODY formation ,SYNTHETIC antibodies ,AMINO acid sequence ,MOLECULAR imprinting ,INDUSTRIAL chemistry ,EDUCATION theory ,SUBJECTIVITY - Abstract
In 1940, Linus Pauling proposed his template theory of antibody formation, one of many such theories that rejected Paul Ehrlich's selective theory of preformed "receptors" (antibodies), assuming instead a direct molding of antibody shapes onto that of the antigen. Pauling believed that protein shapes--independently of amino acid sequences--determined antibody specificity and biological specificity in general. His theory was informed by his pioneering work on protein structure, and it was inspired by the intuitive "rule of parsimony" and simplicity. In 1942, Pauling published his alleged success in producing specific artificial antibodies through experiments based on his 1940 theory. However, his experiments could not be reproduced by prominent immunochemists at the time, and, later, it became generally accepted that antibody specificity was not generated according to Pauling's and others' "instruction" template theories. A citation analysis shows that Pauling's papers on antibody generation continue to be cited as, among other things, pioneering studies of a chemical technology called "molecular imprinting." The examples of Pauling and other protein chemists are used in this paper to demonstrate that scientific belief, philosophical concepts, and subjective theory preferences facilitated the occurrence of irreproducibility in immunochemistry and beyond. The article points to long-term consequences for the scientific community if irreproducible results are not acknowledged. It concludes by arguing that despite the risks, e.g., for the occurrence and perpetuation of irreproducible results that they entail, subjectivity and a commitment to scientific convictions have often been pre-requisites for the generation, and holding on to, scientific innovation in the face of doubt and rejection from the scientific community. [ABSTRACT FROM AUTHOR]
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- 2021
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20. Enzymatically synthesized exopolysaccharide of a probiotic strain Leuconostoc mesenteroides NTM048 shows adjuvant activity to promote IgA antibody responses
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Koji Hosomi, Yasuki Higashimura, Keiko Hisa, Jun Kunisawa, Chiaki Matsuzaki, Ikuto Endo, Kenji Yamamoto, Saki Itonori, Yukari Nakashima, and Yusuke Tomabechi
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Microbiology (medical) ,Genotype ,medicine.medical_treatment ,RC799-869 ,Leuconostoc mesenteroides ,Microbiology ,law.invention ,Mice ,chemistry.chemical_compound ,Probiotic ,adjuvant ,Polysaccharides ,law ,Adjuvanticity ,medicine ,Animals ,IgA antibody ,Strain (chemistry) ,biology ,Probiotics ,Gastroenterology ,Genetic Variation ,Fructose ,Bacterial Infections ,Diseases of the digestive system. Gastroenterology ,biology.organism_classification ,Immunoglobulin A ,Disease Models, Animal ,Infectious Diseases ,chemistry ,Antibody Formation ,biology.protein ,exopolysaccharide ,glucosyltransferase ,Glucosyltransferase ,Adjuvant ,probiotic ,IgA ,Research Article ,Research Paper - Abstract
Leuconostoc mesenteroides strain NTM048 produces an exopolysaccharide (EPS; glucose polymers 94% and fructose polymers 6%) with adjuvanticity for mucosal vaccination. Strain NTM048 includes three putative EPS-synthesizing genes, gtf1 and gtf2 for synthesizing glucose polymers, and lvnS for synthesizing fructose polymer. To elucidate the key polymer structure for adjuvanticity, two genes, gtf1 and gtf2, which were annotated as glycoside hydrolase family 70 enzyme genes, were expressed in Escherichia coli. Glycosyl-linkage composition analysis and NMR analysis showed that the recombinant enzyme Gtf1 produced a soluble form of α-1,6-glucan, whereas the recombinant enzyme Gtf2 produced glucans with approximately equal percentages of α-1,6- and α-1,3-glucose residues both in the supernatant (S-glucan) and as a precipitate (P-glucan). Comparison of polysaccharides synthesized by Gtf1, Gtf2, and LvnS revealed that Gtf2-S-glucan, which was produced in the supernatant by Gtf2 and formed particles of 7.8 µm, possessed 1.8-fold higher ability to stimulate IgA production from murine Peyer’s patch cells than native NTM048 EPS. Evaluation of adjuvanticity by intranasal administration of mice with an antigen (ovalbumin) and Gtf2-S-glucan or NTM048 EPS showed that Gtf2-S-glucan induced the production of higher antigen-specific antibodies in the airway mucosa and plasma, suggesting a pivotal role of Gtf2-S-glucan in the adjuvanticity of NTM048 EPS.
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- 2021
21. Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
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Mar Masiá, Vanesa Agulló, Marta Fernández-González, Lucía Guillén, Félix Gutiérrez, Javier García-Abellán, Guillermo Telenti, José A. García, Piedad Ortega, and Sergio Padilla
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Male ,0301 basic medicine ,viruses ,lcsh:Medicine ,Antibodies, Viral ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Prospective Studies ,Prospective cohort study ,lcsh:R5-920 ,biology ,Interleukin ,General Medicine ,Middle Aged ,Viral Load ,Tocilizumab ,N-IgG ,Titer ,030220 oncology & carcinogenesis ,RNA, Viral ,Female ,Coronavirus Infections ,lcsh:Medicine (General) ,Viral load ,Research Paper ,Pneumonia, Viral ,Antibodies, Monoclonal, Humanized ,General Biochemistry, Genetics and Molecular Biology ,Betacoronavirus ,03 medical and health sciences ,Humans ,Interleukin 6 ,Viral kinetics ,Pandemics ,Aged ,Proportional Hazards Models ,Interleukin-6 ,Proportional hazards model ,business.industry ,SARS-CoV-2 ,lcsh:R ,COVID-19 ,Blockade ,Kinetics ,030104 developmental biology ,chemistry ,S-IgG ,Immunoglobulin G ,Antibody Formation ,Immunology ,Commentary ,biology.protein ,Antibody responses ,Anti-cytokine therapy ,business - Abstract
Background: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. Findings: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0.016) and SARS-CoV-2 viral load (p
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- 2020
22. The genetics of resilience and its relationships with egg production traits and antibody traits in chickens.
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Berghof, Tom V. L., Bedere, Nicolas, Peeters, Katrijn, Poppe, Marieke, Visscher, Jeroen, and Mulder, Han A.
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AGRICULTURAL egg production ,ANTIBODY formation ,PSYCHOLOGICAL resilience ,GENETIC correlations ,CHICKENS ,POULTRY breeding - Abstract
Background: Resilience is the capacity of an animal to be minimally affected by disturbances or to rapidly return to its initial state before exposure to a disturbance. Resilient livestock are desired because of their improved health and increased economic profit. Genetic improvement of resilience may also lead to trade-offs with production traits. Recently, resilience indicators based on longitudinal data have been suggested, but they need further evaluation to determine whether they are indeed predictive of improved resilience, such as disease resilience. This study investigated different resilience indicators based on deviations between expected and observed egg production (EP) by exploring their genetic parameters, their possible trade-offs with production traits, and their relationships with antibody traits in chickens. Methods: Egg production in a nucleus breeding herd environment based on 1-week-, 2-week-, or 3-week-intervals of two purebred chicken lines, a white egg-laying (33,825 chickens) and a brown egg-laying line (34,397 chickens), were used to determine deviations between observed EP and expected average batch EP, and between observed EP and expected individual EP. These deviations were used to calculate three types of resilience indicators for two life periods of each individual: natural logarithm-transformed variance (ln(variance)), skewness, and lag-one autocorrelation (autocorrelation) of deviations from 25 to 83 weeks of age and from 83 weeks of age to end of life. Then, we estimated their genetic correlations with EP traits and with two antibody traits. Results: The most promising resilience indicators were those based on 1-week-intervals, as they had the highest heritability estimates (0.02–0.12) and high genetic correlations (above 0.60) with the same resilience indicators based on longer intervals. The three types of resilience indicators differed genetically from each other, which indicates that they possibly capture different aspects of resilience. Genetic correlations of the resilience indicator traits based on 1-week-intervals with EP traits were favorable or zero, which means that trade-off effects were marginal. The resilience indicator traits based on 1-week-intervals also showed no genetic correlations with the antibody traits, which suggests that they are not informative for improved immunity or vice versa in the nucleus environment. Conclusions: This paper gives direction towards the evaluation and implementation of resilience indicators, i.e. to further investigate resilience indicator traits based on 1-week-intervals, in breeding programs for selecting genetically more resilient layer chickens. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France
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Yoann Madec, François Anna, Sandrine Fernandes-Pellerin, Marie Mielcarek, Olivier Schwartz, Rebecca Grant, Nicolas Collongues, Isabelle Staropoli, David Rey, Alexandre Bolle, Nathalie Jolly, Laura Tondeur, Charlotte Renaudat, Ludivine Grzelak, Nicolas Lefebvre, Marie-Noëlle Ungeheuer, Arnaud Fontanet, Bruno Hoen, Jérôme De Seze, Timothée Bruel, Catherine Schmidt-Mutter, Samira Fafi-Kremer, Aurélie Velay, Pierre Charneau, Philippe Souque, Nicolas Meyer, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), CHU Strasbourg, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Université Paris Cité (UPCité), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys, Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris] (IP), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Groupe Méthodes en Recherche Clinique [Strasbourg] (GMRC), Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Direction de la recherche médicale de l'Institut Pasteur, Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), OS lab is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR- 10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro- Immuno' ANR-14-CE14-0015-01 and the Gilead HIV cure program. LG is supported by the French Ministry of Higher Education, Research and Innovation. SFK lab receives funding from Strasbourg University Hospitals (COVID-HUS, CE-2020-34)., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), univOAK, Archive ouverte, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Appel à projets générique - Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue - - TIMTAMDEN2014 - ANR-14-CE14-0029 - Appel à projets générique - VALID, Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID, Vaccine Research Institute [Créteil, France] (VRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-TheraVectys, Institut Pasteur [Paris], and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE)
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Male ,0301 basic medicine ,Future studies ,MESH: Coronavirus Infections ,[SDV]Life Sciences [q-bio] ,Antibodies, Viral ,Severity of Illness Index ,Neutralization ,Serology ,MESH: Antibodies, Neutralizing ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,MESH: Reverse Transcriptase Polymerase Chain Reaction ,MESH: COVID-19 ,030212 general & internal medicine ,Mild disease ,[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,0303 health sciences ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,MESH: Middle Aged ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,General Medicine ,Middle Aged ,MESH: Hospitals ,Hospitals ,3. Good health ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology ,030220 oncology & carcinogenesis ,MESH: RNA, Viral ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,RNA, Viral ,MESH: Betacoronavirus ,Female ,France ,Sample collection ,Antibody ,Coronavirus Infections ,Research Paper ,Adult ,medicine.medical_specialty ,MESH: Pandemics ,Coronavirus disease 2019 (COVID-19) ,Health Personnel ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Article ,General Biochemistry, Genetics and Molecular Biology ,Antibodies ,Betacoronavirus ,03 medical and health sciences ,Internal medicine ,MESH: Severity of Illness Index ,medicine ,Humans ,Serologic Tests ,MESH: SARS-CoV-2 ,Symptom onset ,Pandemics ,030304 developmental biology ,MESH: Humans ,business.industry ,Mild covid-19 ,SARS-CoV-2 ,MESH: Serologic Tests ,COVID-19 ,MESH: Adult ,Antibodies, Neutralizing ,MESH: Male ,Personnel, Hospital ,MESH: France ,030104 developmental biology ,MESH: Pneumonia, Viral ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Antibody Formation ,biology.protein ,MESH: Health Personnel ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,MESH: Female ,MESH: Antibodies, Viral - Abstract
PMCID: PMC7502660; International audience; BACKGROUND: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized.METHODS: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity). The neutralizing activity of the sera was tested with a pseudovirus-based assay.FINDINGS: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV-2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P = 0.02). INTERPRETATION: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.FUNDINGS: The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.
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- 2020
24. Circulating follicular helper T cells and subsets are associated with immune response to hepatitis B vaccination
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Yan Zhang, Lingfeng Huang, Mingjuan Yin, Jie Zhao, Gang Liu, Jingxiao Huang, Yongzhen Xiong, Jin-Mei Zeng, Jindong Ni, Yi Zhao, Tingyu Lian, Zuwei Yu, and Dong-Mei Liang
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HBsAg ,T Follicular Helper Cells ,T cell ,030231 tropical medicine ,Immunology ,Spleen ,CXCR3 ,CD19 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Immunology and Allergy ,Medicine ,Animals ,030212 general & internal medicine ,Pharmacology ,biology ,business.industry ,Vaccination ,T-Lymphocytes, Helper-Inducer ,BCL6 ,Hepatitis B ,medicine.anatomical_structure ,Antibody Formation ,biology.protein ,business ,Research Paper - Abstract
Around 5–10% of healthy vaccinees lack or produce an inadequate antibody response following receipt of a standard hepatitis B vaccination regimen. Studying immune response to hepatitis B vaccination could promote researches of immunological events contributing to this poor response. To address this, we investigated follicular helper T (Tfh) cells and firstly demonstrated similar kinetics between circulating Tfh (cTfh) cells and Tfh cells derived from mice spleen after hepatitis B vaccination. And cTfh cells were positively associated with anti-HBs at one week after vaccination (D7). Furthermore, we found PBMCs stimulated by HBsAg showed preferential activation of CXCR3(−) Tfh cells subsets in vitro. The expression of transcription factor BCL6 in CD4(+) T cell significantly differed between D7 and four weeks after vaccination (D28). However, dynamic curve of CD19(+) B cells tended to rise then fall but no significant trends were observed. Our findings revealed a decrease in cTfh cells and subset skewing contribute to reduced antibody responses in immune response to hepatitis B vaccination, which indicated the importance of Tfh cell in facilitating the optimization of vaccine efficacy.
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- 2020
25. Analysis of protective immune responses to seasonal influenza vaccination in HIV-infected individuals
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Shenghui Qin, Ying Xia, Guoqiang Du, and Fuli Mi
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Influenza vaccine ,030231 tropical medicine ,Immunology ,HIV Infections ,Antibodies, Viral ,Peripheral blood mononuclear cell ,Neutralization ,Serology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Influenza A Virus, H1N1 Subtype ,Influenza, Human ,Immunology and Allergy ,Medicine ,Humans ,030212 general & internal medicine ,Pharmacology ,biology ,business.industry ,Influenza A Virus, H3N2 Subtype ,Vaccination ,virus diseases ,Apoptosis ,Influenza Vaccines ,Antibody Formation ,biology.protein ,Leukocytes, Mononuclear ,Seasons ,Antibody ,business ,Research Paper - Abstract
Owing to their increased susceptibility to influenza infection, HIV+ individuals are recommended to receive annual influenza vaccination. However, influenza vaccination induced production of anti-influenza neutralization antibodies (Nab) is successful only in some viral-suppressed antiretroviral therapy (ART) treated HIV+ subjects. Additionally, the mechanism of antibody response induced by influenza vaccine in antiretroviral-treated HIV+ subjects is unclear. In this study, we conducted a cohort study which contains 40 HIV+ ART-treated individuals to whom one dose of seasonal influenza vaccine was administered. Blood samples were collected on day 0, 7, 14, and 28 post-vaccination, and serologic responses were characterized by ELISA and micro-neutralization to measure the total antibodies and Nab against influenza vaccines. Transcriptional profiling of peripheral blood mononuclear cells (PBMCs) and immunological assays was measured. Increased levels of proliferation of CD4+T cells and B cells with their corresponding subtypes were observed in HIV-infected subjects at day 7 (D7) following vaccination compared to pre-vaccination. Moreover, proliferation of CD4+T cells and B cells (D7) was correlated with influenza-specific H1N1 Nab at day 28 (D28). Our study could also demonstrate that apoptosis of CD4+T cells and B cells (D7) were inversely correlated with influenza-specific H1N1 Nab. Based on the Nab response after vaccination to each influenza subtypes (D28), HIV+ subjects were stratified as influenza vaccine responders and influenza vaccine non-responders ("responders" ≥ 4-fold increase from day 0; "non-responders" < 4-fold increase from day 0). A selected list of biological pathways (H1N1and H3N2: olfactory transduction, B: phagosome) enriched with transcripts were significantly altered in (ART) treated HIV+ subjects among Nab production responders. This study demonstrated a more detailed mechanism of immune regulation on influenza induced antibody response and revealed some knowledge regarding bioinformatics of vaccine responders and non-responder in influenza induced antibody production in ART-treated HIV patients.
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- 2020
26. Synchrony in serum antibody response to conserved proteins of
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Dabin, Ren, Peter, Bajorski, Timothy F, Murphy, Eric R, Lafontaine, and Michael E, Pichichero
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Otitis Media ,Child, Preschool ,Nasopharynx ,Antibody Formation ,Humans ,Infant ,Child ,Antibodies, Bacterial ,Moraxella catarrhalis ,Bacterial Outer Membrane Proteins ,Research Paper - Abstract
Conserved Moraxella catarrhalis (Mcat) proteins, oligopeptide permease (Opp)A, hemagglutinin (Hag), outer membrane protein (OMP) CD, Pilin A clade 2 (PilA2), and Moraxella surface protein (Msp) 22 have been studied as vaccine candidates. Children who experience frequent acute otitis media (AOM) confirmed with pathogen identification by tympanocentesis are referred to as stringently-defined otitis prone (sOP). Synchrony of serum antibody responses against 5 Mcat proteins, OppA, Hag, OMP CD, PilA2, and Msp22 resulting from nasopharyngeal colonization and AOM was studied for 85 non-otitis prone (NOP) children and 34 sOP children. Changes in serum IgG were quantitated with ELISA. Serum IgG antibody levels against OppA, Hag, OMP CD, and Msp22 rose in synchrony in NOP and sOP children; that is, the proteins appeared equally and highly immunogenic in children at age 6 to 22–25 months old and then leveled off in their rise at 22–25 to 30 months old. In contrast, rises of PilA2 were slow from 6 months old and kept constant and did not level off significantly before 30 months old. OppA, Hag, OMP CD, and Msp22 elicited a synchronous acquisition of naturally-induced serum antibody in young children. A multi-valent Mcat protein vaccine combining OppA, Hag, OMP CD, and Msp22 may exhibit less antigen competition when administered as a combination vaccine in young children.
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- 2020
27. Hamster neogenin, a host-cell protein contained in a respiratory syncytial virus candidate vaccine, induces antibody responses in rabbits but not in clinical trial participants
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Ilse Dieussaert, Marta Picciolato, Ann-Muriel Steff, Bruno André, Koen Maleux, Maria Key Prato, Laurence Fissette, Chanel Cadieux-Dion, Xavier Czeszak, Marc Louckx, Gaël de Lannoy, Walthère Dewé, and Dominique Ingels
- Subjects
vaccine candidate ,viruses ,Placenta ,respiratory syncytial virus ,Antibodies, Viral ,law.invention ,0302 clinical medicine ,law ,Pregnancy ,Cricetinae ,Immunology and Allergy ,030212 general & internal medicine ,Respiratory system ,chemistry.chemical_classification ,Chinese hamster ovary cell ,virus diseases ,respiratory system ,host cell protein ,Recombinant DNA ,Female ,Rabbits ,Research Article ,Research Paper ,Adult ,030231 tropical medicine ,Immunology ,Hamster ,Nerve Tissue Proteins ,Receptors, Cell Surface ,CHO Cells ,Respiratory Syncytial Virus Infections ,Biology ,Virus ,03 medical and health sciences ,Cricetulus ,RSV-PreF ,Respiratory Syncytial Virus Vaccines ,fusion protein ,Animals ,Humans ,Pharmacology ,Neogenin ,Infant, Newborn ,Membrane Proteins ,Fusion protein ,Virology ,Antibodies, Neutralizing ,Chinese hamster ovary ,Immunization ,chemistry ,Respiratory Syncytial Virus, Human ,Antibody Formation ,Glycoprotein ,Viral Fusion Proteins - Abstract
A recombinant respiratory syncytial virus (RSV) fusion glycoprotein candidate vaccine (RSV-PreF) manufactured in Chinese hamster ovary cells was developed for immunization of pregnant women, to protect newborns against RSV disease through trans-placental antibody transfer. Traces of a host-cell protein, hamster neogenin (haNEO1), were identified in purified RSV-PreF antigen material. Given the high amino-acid sequence homology between haNEO1 and human neogenin (huNEO1), there was a risk that potential vaccine-induced anti-neogenin immunity could affect huNEO1 function in mother or fetus. Anti-huNEO1 IgGs were measured by enzyme-linked immunosorbent assay in sera from rabbits and trial participants (Phase 1 and 2 trials enrolling 128 men and 500 non-pregnant women, respectively; NCT01905215/NCT02360475) collected after immunization with RSV-PreF formulations containing different antigen doses with/without aluminum-hydroxide adjuvant. In rabbits, four injections administered at 14-day intervals induced huNEO1-specific IgG responses in an antigen-dose- and adjuvant-dependent manner, which plateaued in the highest-dose groups after three injections. In humans, no vaccination-induced anti-huNEO1 IgG responses were detected upon a single immunization, as the values in vaccine and control groups fluctuated around pre-vaccination levels up to 90/360 days post-vaccination. A minority of participants had anti-huNEO1 levels ≥ assay cutoff before vaccination, which did not increase post-vaccination. Thus, despite detecting vaccine-induced huNEO1-specific responses in rabbits, we found no evidence that the candidate vaccine had induced anti-huNEO1 immunity in human adults. The antigen purification process was nevertheless optimized, and haNEO1-reduced vaccines were used in a subsequent Phase 2 trial enrolling 400 non-pregnant women (NCT02956837), in which again no vaccine-induced anti-huNEO1 responses were detected.
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- 2020
28. A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children
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María Marcó del Pont, Lorena I. Gimenez, Norberto De Carli, Maria Laura Polo, Laura Alvarez, Melina Salvatori, Jorge Geffner, Augusto Varese, Juan Martín Gómez Penedo, Silvina Raiden, Eugenia M. Takata, María Revetria, Ana L. Alcalde, María Temis Agosta, Patricia Coll, Hernán Pérez, Macarena Uranga, Nancy Simaz, Constanza Russo, Mariela García, Patricia G Suárez, Ana Ceballos, Carola Bayle, Fernando Ferrero, María J. Chiolo, Susana Villa Nova, María José Rolón, Lourdes Arruvito, Héctor Cairoli, Mariam Sarli, Sandra Di Lalla, Inés Sananez, Emilia Cohen, Graciela Mosquera, Gabriela Gregorio, Jorge Lattner, Nicolás A. Grisolía, Claudia Meregalli, María J. Bruera, María P. Holgado, Silvia C. Algieri, Mariela F. Pérez, Valeria Nivela, Vanesa Seery, Claudio Piccardo, Patricia Tuccillo, Daniela Filippo, Myriam Nuñez, and Carolina Davenport
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Male ,Medicine (General) ,Disease severity, antibodies, T cells ,Argentina ,Disease ,Antibodies, Viral ,medicine.disease_cause ,Asymptomatic ,General Biochemistry, Genetics and Molecular Biology ,Immunoglobulin G ,R5-920 ,Humans ,Medicine ,Child ,Coronavirus ,biology ,SARS-CoV-2 ,business.industry ,COVID-19 ,Infant ,General Medicine ,medicine.disease ,Systemic Inflammatory Response Syndrome ,Pediatric COVID-19 ,Systemic inflammatory response syndrome ,Immunoglobulin M ,Child, Preschool ,Antibody Formation ,Immunology ,Cohort ,biology.protein ,Cytokines ,Female ,medicine.symptom ,Antibody ,business ,Research Paper - Abstract
Background Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown. Methods We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods. Findings Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines. Interpretation A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease. Funding National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548).
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- 2021
29. Immunogenicity and safety of a novel seasonal influenza preservative-free vaccine manufactured in Kazakhstan: Results of a randomized, comparative, phase II clinical trial in adults
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Ilyas Кulmagambetov, Yevgeniy Volgin, Marina Stukova, Timur Issagulov, Berik Khairullin, Timur Davlyatshin, Abylay Sansyzbay, Gulbanu Sarsenbayeva, Nikolay Bogdanov, Zhanna Buzitskaya, and Markhabat Kassenov
- Subjects
Male ,medicine.medical_specialty ,030231 tropical medicine ,Immunology ,Antibodies, Viral ,Comparative evaluation ,Seasonal influenza ,03 medical and health sciences ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Internal medicine ,Influenza, Human ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Preservative free ,Pharmacology ,business.industry ,Influenza A Virus, H3N2 Subtype ,Immunogenicity ,Preservatives, Pharmaceutical ,Vaccination ,Hemagglutination Inhibition Tests ,Kazakhstan ,Clinical trial ,Influenza B virus ,Vaccines, Inactivated ,Influenza Vaccines ,Antibody Formation ,Female ,Seasons ,business ,Research Paper - Abstract
Background: The study was aimed at comparative evaluation of seasonal influenza vaccine RIBSP versus commercial vaccine VAXIGRIP® for immunogenicity and safety in the course of clinical trial phase II on healthy volunteers aged 18–60 years. Methods: The trial involved 150 subjects in randomized 2:1 groups that received either RIBSP vaccine or comparator vaccine VAXIGRIP®. One dose (0.5 ml) of either vaccine contained 15 μg of hemagglutinin of each influenza virus strain recommended by WHO for the Northern hemisphere in 2016–2017 flu season. The observation period lasted 21 day. The trial was registered at ClinicalTrials.gov identifier NCT 03016143. Results: Assessment of immunogenic activity of the vaccine under study showed that in 21 day the portion of participants with 4-fold seroconversions was 87.0% to A/H1N1; 63.0% to A/H3N2 and 59.0% to B virus. Antibody titer increase factor in the group of subjects that received RIBSP vaccine was 23.3 for A/H1N1; 4.4 for A/H3N2 and 4.5 for B virus. The volunteers that received RIBSP vaccine demonstrated 95% seroprotection level against A/H1N1; 84% against A/H3N2 and 80% against B virus. RIBSP vaccine met the CHMP criteria of the Committee for Medicinal Products for Human Use (CPMP/BWP/214/96). In the course of evaluating the vaccine safety no serious undesirable effects were recorded. All changes of laboratory data were slight and single in most cases. All recorded local reactions have been light in character and these have been predicted reactions observed at vaccination against influenza. Conclusion: Comparison of the allantoic inactivated split vaccine obtained in vaccines RIBSP and VAXIGRIP®, showed similar immunogenic activity. Both vaccines were safe for the study participants.
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- 2017
30. The dynamics of immunoglobulin V-gene usage and clonotype expansion in mice after prime and boost immunizations as analyzed by NGS
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Shixia Wang, Diego J. Farfán-Arribas, Shan Lu, and Shuying Liu
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DNA vaccine ,0301 basic medicine ,Immunologic Factors ,animal diseases ,Immunology ,Immunoglobulin Variable Region ,chemical and pharmacologic phenomena ,Computational biology ,Biology ,germline ,DNA sequencing ,DNA vaccination ,03 medical and health sciences ,vaccine ,Immunoglobulin ,Animals ,Immunology and Allergy ,Gene ,Pharmacology ,B-Lymphocytes ,Vaccines ,Repertoire ,High-Throughput Nucleotide Sequencing ,biochemical phenomena, metabolism, and nutrition ,Research Papers ,Mice, Inbred C57BL ,030104 developmental biology ,Antibody Formation ,Next-generation sequencing ,V-gene ,biology.protein ,bacteria ,Female ,Antibody ,Antibody formation ,Immunoglobulin V - Abstract
In the current study, an improved NGS approach was developed to study the B-cell repertoire evolution in a simple mouse immunization model including only two DNA immunizations. The combination of 5′RACE and Ion Torrent long reads enabled unbiased immunoglobulin repertoire analysis even from small amounts of peripheral mouse blood. The B-cell population expanded by the vaccine displayed a relatively strong clonality. Upon priming with the first vaccine dose, we observed a consistent pattern of V-segment gene and CDR3 usage (public specificities). Interestingly, this pattern diversified with the second dose of immunization —it was relatively different in individual mice in spite of having received the same vaccine regimen (private specificities). Nevertheless, there were several instances in which the same public V-segment genes and CDR3s that were expanded after the first dose were further amplified after the second immunization. Taken together, it appears that the major clonotypes expanded by vaccination were originally a homogeneous subset that later diversified after a second dose leading to diverse “private” clonal compositions in different mice. These results established a new platform valuable to perform longitudinal analyses of the Ig germline gene usage and clonotype evolution throughout an immunization regimen in a commonly used animal model.
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- 2017
31. Biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the humoral immunoresponse: a systematic review of evidence to support global policy-level actions and research.
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Nair, Shalini and Xinguang Chen
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ONLINE information services ,HEALTH policy ,COVID-19 ,SYSTEMATIC reviews ,SERODIAGNOSIS ,MOLECULAR pathology ,ANTIBODY formation ,MOLECULAR biology ,SEVERITY of illness index ,DECISION making ,SARS virus ,MEDLINE ,VIRAL antibodies ,COVID-19 testing - Abstract
Background: Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019 (COVID-19) pandemic. Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a paucity of systemized data on this subject. Objective: In this review, we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies. We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity, transmission potential, and prognosis. Data Sources and Methods: Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications. Search terms included: "Novel Coronavirus" OR "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" AND "Immunity" OR "Immune Response" OR "Antibody Response" OR "Immunologic Response". Studies published from December 31, 2019 to December 31, 2020 were included. To ensure validity, papers in pre-print were excluded. Results: Of 2 889 identified papers, 36 were included. Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2. Antibody titers appear to markedly increase two weeks after infection, followed by a plateau. A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations. This trend persists with regard to the length of antibody maintenance. However, overall immunity appears to wane within two to three months post-infection. Conclusion: Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection. Immunity generated through natural infection appears to be short, suggesting a need for long-term efforts to control the pandemic. Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention. Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity. [ABSTRACT FROM AUTHOR]
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- 2022
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32. An apolipoprotein B100 mimotope prevents obesity in mice
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Hyun Kyun Na, Young Sik Kim, Hyo Joon Kim, Jemin Han, Hae Jung Joung, Jung Soon Choi, Bert Binas, Ji Young Kim, and Hee Jong Lee
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Male ,0301 basic medicine ,medicine.medical_specialty ,Apolipoprotein B ,Lipolysis ,Diet, High-Fat ,Immunoglobulin G ,S4 ,Rats, Sprague-Dawley ,Epitopes ,Mice ,03 medical and health sciences ,humoral immunity ,Internal medicine ,medicine ,high-fat-diet-induced obesity ,Animals ,Obesity ,Hypolipidemic Agents ,Foam cell ,Original Paper ,Mice, Inbred BALB C ,Mice, Inbred ICR ,biology ,Mimotope ,mimotope ,ApoB100 ,Fatty liver ,General Medicine ,medicine.disease ,Original Papers ,Rats ,Fatty Liver ,Lipoproteins, LDL ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Antibody Formation ,Apolipoprotein B-100 ,Immunology ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Anti-Obesity Agents ,Antibody ,Peptides ,Lipoprotein - Abstract
Immunization with an ApoB100 mimotope prevents high-fat-diet-induced obesity in mice. Antibody titres parallel the weight decrements. In vitro data implicate increased lipolysis and reduced lipoprotein uptake by adipocytes, as well as increased uptake and metabolism of native lipoprotein by macrophages., Although apolipoprotein B100 (ApoB100) plays a key role in peripheral fat deposition, it is not considered a suitable therapeutic target in obesity. In the present study we describe a novel ApoB100 mimotope, peptide pB1, and the use of pB1-based vaccine-like formulations (BVFs) against high-fat diet (HFD)-induced obesity. In HFD- compared with chow-fed adolescent mice, BVFs reduced the 3-month body-weight gains attributable to increased dietary fat by 44–65%, and prevented mesenteric fat accumulation and liver steatosis. The body-weight reductions paralleled the titres of pB1-reactive immunoglobulin G (IgG) antibodies, and pB1-reactive antibodies specifically recognized native ApoB100 and a synthetic peptide from the C-terminal half of ApoB100. In cultured 3T3L1 adipocytes, anti-pB1 antibodies increased lipolysis and inhibited low-density lipoprotein (LDL) uptake. In cultured RAW 264.7 macrophages, the same antibodies enhanced LDL uptake (without causing foam cell formation). These findings make ApoB100 a promising target for an immunization strategy against HFD-induced obesity.
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- 2015
33. Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice
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Sidhartha Chaudhury, Daniel R. Ripoll, Connie S. Schmaljohn, Mariano Sanchez-Lockhart, Katya Shimanovskaya, Anders Wallqvist, Daniel A. J. Mitchell, Jaap W. Back, Lesley C. Dupuy, and Gustavo Palacios
- Subjects
filovirus ,DNA vaccine ,focusing ,0301 basic medicine ,Subdominant ,mice ,medicine.drug_class ,030106 microbiology ,Immunology ,Biology ,Antibodies, Viral ,Monoclonal antibody ,medicine.disease_cause ,Epitope ,DNA vaccination ,Ebola virus ,Epitopes ,03 medical and health sciences ,antibody ,Vaccines, DNA ,medicine ,Animals ,Immunology and Allergy ,Ebola Vaccines ,Antigens, Viral ,Immunization Schedule ,Glycoproteins ,Pharmacology ,Mice, Inbred BALB C ,Vaccines, Synthetic ,Linear epitope ,Ebolavirus ,Research Papers ,Virology ,epitope mapping ,030104 developmental biology ,Epitope mapping ,Antibody Formation ,DNA, Viral ,biology.protein ,Antibody - Abstract
We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed 2 DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP. Although a construct designed to produce a membrane-bound oligopeptide was poorly immunogenic, a construct generating a secreted oligopeptide elicited strong antibody responses in mice. When this construct was administered as a boost to a DNA vaccine expressing the complete EBOV GP gene, the resultant antibody response was focused largely toward the less immunodominant epitopes in the oligopeptide. Taken together, the results of this work suggest a utility for this method for immune focusing of antibody responses elicited by vaccination.
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- 2017
34. A cancer vaccine based on fluorine-modified sialyl-Tn induces robust immune responses in a murine model
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Chengcheng Song, Chang-Cheng Liu, Xiu-Jing Zheng, Yifa Zhou, and Xin-Shan Ye
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Cytotoxicity, Immunologic ,0301 basic medicine ,glycoconjugate vaccine ,medicine.medical_treatment ,tumor-associated carbohydrate antigen ,chemical and pharmacologic phenomena ,complex mixtures ,Cancer Vaccines ,Immune tolerance ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Adjuvants, Immunologic ,Cancer immunotherapy ,Antigen ,T-Lymphocyte Subsets ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Antigens, Tumor-Associated, Carbohydrate ,cross reaction ,Immunity, Cellular ,cancer immunotherapy ,business.industry ,Immunogenicity ,Antibody-Dependent Cell Cytotoxicity ,Immunity ,hemic and immune systems ,Fluorine ,Immunotherapy ,Disease Models, Animal ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Antibody Formation ,Immunology ,Female ,Immunization ,Cancer vaccine ,fluoro-substituted STn ,business ,therapeutics ,Adjuvant ,Research Paper - Abstract
// Chengcheng Song 1, 2 , Xiu-Jing Zheng 1 , Chang-Cheng Liu 1 , Yifa Zhou 2 and Xin-Shan Ye 1 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China 2 School of Life Sciences, Northeast Normal University, Changchun 130024, China Correspondence to: Xin-Shan Ye, email: xinshan@bjmu.edu.cn Yifa Zhou, email: zhouyf383@nenu.edu.cn Keywords: cancer immunotherapy, glycoconjugate vaccine, tumor-associated carbohydrate antigen, fluoro-substituted STn, cross reaction Received: March 08, 2017 Accepted: April 19, 2017 Published: May 07, 2017 ABSTRACT Development of an effective vaccine to target tumor associated carbohydrate antigens, aberrantly expressed on the cell surface of various carcinomas, is an appealing approach toward cancer immunotherapy. However, a major problem of carbohydrate antigens is their poor immunogenicity. Immunization with modified-carbohydrate antigens could improve the immunogenicity and induce cross reaction with the native carbohydrate antigens. In this study, we investigated the antitumor ability of three fluoro-substituted sialyl-Tn (STn) analogues (2, 3, 4) coupled to KLH (keyhole limpet hemocyanin) and studied the mechanism of tumor immunotherapy of the vaccines in a murine model of colon cancer. Vaccination with 4-KLH, in which the two N -acetyl groups of STn are substituted with N -fluoroacetyl groups, could remarkably prolong the survival of tumor-bearing mouse and resulted in a significant reduction in tumor burden of lungs compared with STn-KLH (1-KLH). The vaccine 4-KLH could provoke stronger cytotoxic T lymphocytes immune response, T helper (Th) cell-mediated immune response and an earlier-stage Th1 immune response than 1-KLH, thus breaking immune tolerance and generating a therapeutic response. The 4-KLH vaccine induced strong tumor-specific anti-STn antibodies which could mediate complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity against human tumor cells. Moreover, in the absence of adjuvant, 4-KLH still elicited stronger immune responses than 1-KLH. Our data suggested that 4-KLH is superior in tumor prevention. The strategic hapten fluorination may be a potential approach applicable to the vaccines development for the cancer immunotherapy.
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- 2017
35. A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus
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David M. Roth, Duncan A. Gordon, W. Winn Chatham, J Fettiplace, A Chadha, Damon Bass, and C Kleoudis
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Adult ,Male ,medicine.medical_specialty ,Antibodies, Monoclonal, Humanized ,Serogroup ,Pneumococcal Vaccines ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,Rheumatology ,Open label study ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,In patient ,030212 general & internal medicine ,Autoantibodies ,030203 arthritis & rheumatology ,business.industry ,Vaccination ,Autoantibody ,Middle Aged ,Belimumab ,Papers ,Antibody Formation ,Pneumococcal vaccination ,Pneumococcal ,Female ,belimumab ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11–23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little difference was observed between cohorts across a broad response, up to 23 serotypes. Eight (23.5%) patients experienced an adverse event considered by the investigator to be treatment-related in the pre-belimumab cohort and four (8.9%) in the belimumab-concurrent cohort; seven patients experienced non-fatal serious adverse events (pre-belimumab cohort, 11.8% [ n = 4]; concurrent-belimumab cohort, 6.7% [ n = 3]), and no deaths were reported. Conclusion The proportion of patients generating a response to ≥1 pneumococcal serotype did not differ between the pre-belimumab and belimumab-concurrent cohorts; the proportions were also comparable across a broader response (from ≥2 serotypes to 23 serotypes).
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- 2017
36. Serological response to trivalent inactivated influenza vaccine in HIV-infected adults in Singapore
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Eng Eong Ooi, Lay-Hoon Tang, Yuk-Fai Lau, David C. Lye, and Yee Sin Leo
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Adult ,CD4-Positive T-Lymphocytes ,Male ,Volunteers ,0301 basic medicine ,Influenza vaccine ,Immunology ,Population ,Enzyme-Linked Immunosorbent Assay ,HIV Infections ,Peripheral blood mononuclear cell ,Young Adult ,03 medical and health sciences ,Influenza, Human ,Humans ,Immunology and Allergy ,Medicine ,Avidity ,education ,Aged ,Pharmacology ,Singapore ,education.field_of_study ,Hemagglutination assay ,business.industry ,Immunogenicity ,virus diseases ,Hemagglutination Inhibition Tests ,Middle Aged ,Research Papers ,Virology ,Vaccination ,Titer ,030104 developmental biology ,Influenza Vaccines ,Antibody Formation ,Cytokines ,Female ,business - Abstract
A cohort of 81 HIV-infected participants received seasonal trivalent inactivated influenza vaccine (TIV) and their humoral responses were monitored using hemagglutination inhibition (HAI) assay and enzyme-linked immunosorbent assay (ELISA). Three weeks after the vaccination, the percentage of the cohort that had an HAI titer of >1:40 was 35% (for H1N1), 43% (for H3N2) and 19% (for influenza B). An increase in HAI titer can be achieved by an increase in magnitude of the antibody responses, which can be measured by an increase in ELISA titer; as well as a quality improvement of the antibody responses through increased avidity to the virus. For some individuals, an increase in avidity alone is sufficient to reach the sero-protective titer. Notably, a number of volunteers showed an increase in ELISA titer without a rise in HAI titer. A total of 24 participants (30%) did not show any significant increase in both HAI and ELISA tests after vaccination. Apart from a lower peripheral CD4+ T cell count, the non responders' peripheral blood mononuclear cells (PBMC) also had a higher IL-10 mRNA expression after TIV vaccination ex vivo. Cytokine profiling demonstrated that, apart from a weaker MCP-1 expression in the non-responder group, PBMC from both groups responded comparably to lipopolysaccharide (LPS) stimulation in vitro. Since only 3 participants developed sero-protective titers against all 3 subtypes after vaccination, our study highlights a need to enhance the immunogenicity of the subunit vaccine for this population, potentially through harnessing the innate immunity with an external adjuvant.
- Published
- 2017
37. Immunogenicity and safety of an adjuvanted herpes zoster subunit candidate vaccine in adults ≥ 50 years of age with a prior history of herpes zoster: A phase III, non-randomized, open-label clinical trial
- Author
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Katrijn Grupping, Martine Douha, Martina Kovac, Olivier Godeaux, Himal Lal, Thomas C. Heineman, Daniel Shu, and Laura Campora
- Subjects
safety ,CD4-Positive T-Lymphocytes ,Male ,0301 basic medicine ,Herpesvirus 3, Human ,medicine.medical_specialty ,zoster vaccine ,Drug-Related Side Effects and Adverse Reactions ,Immunology ,herpes zoster ,Enzyme-Linked Immunosorbent Assay ,immunogenicity ,Antibodies, Viral ,medicine.disease_cause ,03 medical and health sciences ,Immunogenicity, Vaccine ,0302 clinical medicine ,Adjuvants, Immunologic ,Viral Envelope Proteins ,Internal medicine ,medicine ,Herpes Zoster Vaccine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Adverse effect ,Aged ,Pharmacology ,varicella-zoster virus ,business.industry ,Immunogenicity ,Varicella zoster virus ,Middle Aged ,Research Papers ,Confidence interval ,Vaccination ,Clinical trial ,030104 developmental biology ,Antibody Formation ,Vaccines, Subunit ,Female ,Zoster vaccine ,Open label ,business ,medicine.drug - Abstract
This phase III, non-randomized, open-label, multi-center study (NCT01827839) evaluated the immunogenicity and safety of an adjuvanted recombinant subunit herpes zoster (HZ) vaccine (HZ/su) in adults aged ≥ 50 y with prior physician-documented history of HZ. Participants (stratified by age: 50–59, 60–69 and ≥ 70 y) received 2 doses of HZ/su 2 months apart and were followed-up for another 12 months. Anti-glycoprotein E (gE) antibodies were measured by enzyme-linked immunosorbent assay before vaccination and 1 month after the second dose (Month 3). Solicited local and general adverse events (AEs) were recorded for 7 d and unsolicited AEs for 30 d after each vaccination. Serious AEs were recorded until study end. The primary immunogenicity objective was met if the lower limit of the 95% confidence interval (CI) of the vaccine response rate (VRR), defined as a 4-fold increase in anti-gE over baseline, at Month 3 was ≥ 60%. 96 participants (32/age group) were enrolled. The primary immunogenicity objective was met, as the VRR at Month 3 was 90.2% (95% CI: 81.7–95.7). Geometric mean anti-gE antibody concentrations at Month 3 were similar across age groups. 77.9% and 71.6% of participants reported local and general solicited AEs, respectively. The most frequent solicited AEs were pain at injection site, fatigue, headache, myalgia and shivering. The HZ/su vaccine was immunogenic in adults aged ≥ 50 y with a physician-documented history of HZ, and no safety concerns were identified.
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- 2017
38. The assessment of Hantaan virus-specific antibody responses after the immunization program for hemorrhagic fever with renal syndrome in northwest China
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Hanyu Zeng, Yingfeng Lei, Ying Ma, Linfeng Cheng, Boquan Jin, Zhuo Li, Lihua Chen, Fanglin Zhang, Yusi Zhang, and Ying Wang
- Subjects
Adult ,Male ,0301 basic medicine ,China ,Time Factors ,Adolescent ,Immunology ,Population ,Antibodies, Viral ,Immunoglobulin G ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,education ,Neutralizing antibody ,Hantaan virus ,Pharmacology ,education.field_of_study ,biology ,Immunization Programs ,business.industry ,Viral Vaccines ,Middle Aged ,Antibodies, Neutralizing ,Research Papers ,Virology ,Vaccination ,030104 developmental biology ,Immunoglobulin M ,Hemorrhagic Fever with Renal Syndrome ,Antibody Formation ,Humoral immunity ,biology.protein ,Female ,Antibody ,business - Abstract
Xianyang city is one of the main hemorrhagic fever with renal syndrome (HFRS) epidemic areas in northwest China. Although the HFRS immunity program has been provided in this city, HFRS is still occurred every year. In order to implement the vaccination program effectively and to control HFRS, the analysis of antibody responses specific to Hantaan virus (HTNV) in individuals after vaccination is essential. In this study, a total of 100 subjects were divided into 5 groups: unvaccinated, 1, 3, 29 and 33 months after boost vaccination. The levels and the positive rates of HTNV-NP-specific IgM and IgG antibodies as well as HTNV neutralizing antibodies were significantly increased in the serum of the vaccinated individuals. The positive rates and levels of HTNV-NP-specific IgG and HTNV neutralizing antibody reached their highest values at 3 months respectively and could be sustained up to 33 months after vaccination. Moreover, the titres of HTNV-NP-specific IgM or IgG antibody and the titres of HTNV neutralizing antibody at 1 month after vaccination have a positive correlation. The level of HTNV-NP-specific IgG antibody was much higher than that of HTNV-NP-specific IgM antibody or HTNV neutralizing antibody. In addition, the strongest responses of antibody-secreting cells were observed at 3 months after vaccination, which was consistent with the serum results. Therefore, the HFRS immunization program is effective to induce humoral immunity in the population of northwest China.
- Published
- 2016
39. Adjuvant effect of enterotoxigenic
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Hyesuk, Seo, Ti, Lu, Sachin, Mani, A Louis, Bourgeois, Richard, Walker, David A, Sack, and Weiping, Zhang
- Subjects
Hot Temperature ,Escherichia coli Vaccines ,Escherichia coli Proteins ,Bacterial Toxins ,Dmlt ,antibody response ,Antibodies, Bacterial ,dose effect ,enterotoxigenic Escherichia coli (ETEC) ,Enterotoxins ,Mice ,adjuvant ,Antibody Formation ,CFA/I/II/IV MEFA ,Animals ,Enterotoxigenic Escherichia coli ,Escherichia coli Infections ,Research Paper - Abstract
Double-mutant heat-labile toxin (dmLT, LTR192G/L211A) of enterotoxigenic Escherichia coli (ETEC) is an effective mucosal adjuvant. Recent studies have shown that dmLT also exhibits adjuvanticity for antigens administered parenterally. In this study, we subcutaneously (SC) immunized mice with the ETEC adhesin-based vaccine, CFA/I/II/IV MEFA (multiepitope fusion antigen), adjuvanted with dmLT and examined the impact of dmLT on antibody responses specific to the seven adhesins in the vaccine construction [CFA/I, CFA/II (CS1, CS2, CS3) and CFA/IV (CS4, CS5, CS6)]. Mice were immunized with a fixed dose of CFA/I/II/IV MEFA and ascending doses of dmLT adjuvant (0, 0.05, 0.1, 0.5 or 1.0 µg) to assess the potential dmLT dose response relationship. Data showed that dmLT enhanced systemic antibody responses to all seven antigens (CFA/I, CS1-CS6) targeted by MEFA in a dose-dependent way. The adjuvant effect of dmLT on the MEFA construct plateaued at a dose of 0.1 µg. Results also indicated that dmLT is an effective parenteral adjuvant when given by the SC route with the ETEC adhesin MEFA vaccine and that antibody enhancement was achieved with relatively low doses. These observations suggest the potential usefulness of dmLT for parenteral ETEC vaccine candidates and also perhaps for vaccines against other pathogens.
- Published
- 2019
40. Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies
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Rebecca J. Dearman, Shahid Uddin, Adrian Podmore, Stephen Bishop, Maryam Shah, Jeremy P. Derrick, Ian Kimber, Shraddha S. Rane, and Alain Pluen
- Subjects
Pharmaceutical Science ,02 engineering and technology ,immunogenicity ,030226 pharmacology & pharmacy ,law.invention ,Mice ,0302 clinical medicine ,law ,Pharmacology (medical) ,Immunogenetic Phenomena ,Mice, Inbred BALB C ,biology ,Chemistry ,Immunogenicity ,aggregation ,Antibodies, Monoclonal ,adaptive immunity ,021001 nanoscience & nanotechnology ,Acquired immune system ,Recombinant Proteins ,Cell biology ,host cell impurity ,Recombinant DNA ,Molecular Medicine ,Female ,Antibody ,0210 nano-technology ,Research Paper ,Protein Binding ,Biotechnology ,medicine.drug_class ,Monoclonal antibody ,03 medical and health sciences ,Protein Aggregates ,Immune system ,Heat shock protein ,medicine ,Animals ,HSP70 Heat-Shock Proteins ,Pharmacology ,Organic Chemistry ,Hsp70 ,monoclonal antibody ,Antibody Formation ,biology.protein ,Stress, Mechanical ,Heat-Shock Response - Abstract
Purpose Anti-drug antibodies can impair the efficacy of therapeutic proteins and, in some circumstances, induce adverse health effects. Immunogenicity can be promoted by aggregation; here we examined the ability of recombinant mouse heat shock protein 70 (rmHSP70) - a common host cell impurity - to modulate the immune responses to aggregates of two therapeutic mAbs in mice. Methods Heat and shaking stress methods were used to generate aggregates in the sub-micron size range from two human mAbs, and immunogenicity assessed by intraperitoneal exposure in BALB/c mice. Results rmHSP70 was shown to bind preferentially to aggregates of both mAbs, but not to the native, monomeric proteins. Aggregates supplemented with 0.1% rmHSP70 induced significantly enhanced IgG2a antibody responses compared with aggregates alone but the effect was not observed for monomeric mAbs. Dendritic cells pulsed with mAb aggregate showed enhanced IFNγ production on co-culture with T cells in the presence of rmHSP70. Conclusion The results indicate a Th1-skewing of the immune response by aggregates and show that murine rmHSP70 selectively modulates the immune response to mAb aggregates, but not monomer. These data suggest that heat shock protein impurities can selectively accumulate by binding to mAb aggregates and thus influence immunogenic responses to therapeutic proteins. Electronic supplementary material The online version of this article (10.1007/s11095-019-2586-7) contains supplementary material, which is available to authorized users.
- Published
- 2019
41. Age-related changes in B cell metabolism
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Larissa H. Haut, Kenneth E. Schmader, Hildegund C.J. Ertl, and Raj K. Kurupati
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Adult ,Male ,medicine.medical_specialty ,Aging ,Oxidative phosphorylation ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Carnitine palmitoyltransferase 1 ,B cell metabolism ,Internal medicine ,medicine ,Humans ,Glycolysis ,antibody responses ,B cell ,030304 developmental biology ,Aged ,chemistry.chemical_classification ,Aged, 80 and over ,0303 health sciences ,Reactive oxygen species ,B-Lymphocytes ,biology ,Sirtuin 1 ,Cell Biology ,Metabolism ,vaccination ,3. Good health ,medicine.anatomical_structure ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,Antibody Formation ,biology.protein ,Female ,Energy Metabolism ,Research Paper - Abstract
Antibody responses to vaccinations or infections decline upon aging. In this study we tested if metabolic changes in B cells may contribute to attenuation of responses to influenza vaccination in aged humans. Our data show that aging affects mitochondrial functions in B cells leading to increases in mitochondrial reactive oxygen species (MROS) and mitochondrial mass (MM) in some aged B cell subsets and decreases in expression levels of Sirtuin 1 (SIRT1), Forkhead box protein (FOX)O1 and carnitine palmitoyltransferase 1 (CPT-1). Seahorse analyses showed minor defects in glycolysis in the aged B cells after activation but a strong reduction in oxidative phosphorylation. The analyses of the transcriptome revealed further pronounced defects in one-carbon metabolism, a pathway that is essential for amino acid and nucleotide metabolism. Overall our data support the notion that the declining ability of aged B cells to increase their metabolism following activation contributes to the weakened antibody responses of the elderly.
- Published
- 2019
42. Kinetics of serum antibodies in response to infection with Yersinia enterocolitica
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I Vaitkeviciute, Peter Teunis, Karen A. Krogfelt, and W van Pelt
- Subjects
Adult ,Male ,Serum ,0301 basic medicine ,Gastrointestinal infection ,Yersinia Infections ,Epidemiology ,Denmark ,030106 microbiology ,serology ,Enzyme-Linked Immunosorbent Assay ,Yersinia ,Asymptomatic ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Humans ,Medicine ,Longitudinal Studies ,030212 general & internal medicine ,Seroconversion ,Yersinia enterocolitica ,seroconversion rates ,Original Paper ,biology ,business.industry ,Middle Aged ,Models, Theoretical ,biology.organism_classification ,Antibodies, Bacterial ,Enteritis ,Immunoglobulin A ,Infectious Diseases ,Immunoglobulin M ,Immunoglobulin G ,Antibody Formation ,Immunology ,biology.protein ,Female ,Antibody ,medicine.symptom ,business - Abstract
Information on the kinetics of the serum antibody response to infection with Yersinia enterocolitica is essential to allow the estimation and comparison of seroconversion rates in a diversity of pools of cross-sectional serum antibody measurements. Data from 94 patients with acute enteritis caused by Yersinia infection were used. The follow-up period for the longitudinal study was 36 months, addressed by questionnaire. An indirect enzyme-linked immunosorbent assay method was adapted to determine the concentration of antibodies against Y. enterocolitica in human sera. A mathematical within-host model was used to describe the interaction between pathogen and immune system and the waning of immunity after clearing of the pathogen. All observed antibodies (IgG, IgM, IgA) reached peak levels shortly after infection and then decayed slowly indicating that the median levels decreased only little during the observation period. Estimated maximum peak antibody levels were highest in IgG. Seroresponse curves of all antibodies showed large individual variation between patients. There was no apparent pattern of variation with age, nor any notable difference between genders. Estimated half-times were very long for all antibodies, and their posterior distributions were highly skewed. IgA appeared to have the most persistent antibody response, compared with IgG and IgM. Median peak levels of all three antibodies were similar. There was no significance found between peak antibody levels and severity of symptoms of gastrointestinal infection and severity of joint pain. Our findings allow the use of cross-sectional serum antibody measurements as biomarkers, to estimate seroconversion rates. Such seroincidence estimates include asymptomatic seroconversions, thereby avoiding under-reporting, and allows the comparison of infection pressures among countries, independent of their healthcare and surveillance systems.
- Published
- 2019
43. Dose selection for biological enzyme replacement therapy indicated for inborn errors of metabolism.
- Author
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Hon, Yuen Yi, Wang, Jie, Abodakpi, Henrietta, Balakrishnan, Anand, Pacanowski, Michael, Chakder, Sushanta, Smpokou, Patroula, Donohue, Kathleen, and Wang, Yow‐Ming C.
- Subjects
INBORN errors of metabolism ,ENZYME replacement therapy ,BIOLOGICAL products ,IMMUNOLOGICAL tolerance ,ANTIBODY formation - Abstract
This paper summarizes key features of the dose‐finding strategies used in the development of 11 approved new molecular entities that are first‐in‐class enzyme replacement therapy (ERT), with a goal to gain insight into the dose exploration approaches to inform efficient dose‐finding in future development of biological products for Inborn Errors of Metabolism (IEM). Dose exploration should preferably begin in in vitro studies, followed by testing multiple doses in an appropriate animal disease model, when available, which can provide important information for dose assessment in humans. Performing adequate dose‐finding in early phase clinical studies in a well‐defined study population, including pediatric subjects, is generally critical to inform dose selection for pivotal trials; alternatively, additional dose exploration can be incorporated as part of a pivotal trial. Two important considerations for successful dose selection include (1) identifying appropriate disease‐specific endpoints, including pharmacodynamic (PD) end points and intermediate clinical end points or clinical end points, and (2) designing a study with adequate treatment durations for evaluating these end points. Appropriately selected PD biomarkers is useful for dose selection, and early development of these biomarkers can facilitate the overall clinical development program. Optimization of ERT doses, as well as evaluations of patient intrinsic factors and/or immune tolerance strategies may be necessary to overcome antibody responses or increase efficacy in IEM. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients
- Author
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Luca Cannizzaro, Laura M. Hurley, Anna Innocenzi, Sheila María Álvarez-Fernández, Francesca Sanvito, Antonio Conti, Marco Barbariga, Massimo Alessio, Carlo Vittorio Cannistraci, Alan Zanardi, Nicolò Pecorelli, Marco Braga, Álvarez-Fernández, S, Barbariga, M, Cannizzaro, L, Cannistraci, C, Hurley, L, Zanardi, A, Conti, A, Sanvito, F, Innocenzi, A, Pecorelli, N, Braga, M, Alessio, M, Alvarez-Fernandez, S. M., Barbariga, M., Cannizzaro, L., Cannistraci, C. V., Hurley, L., Zanardi, A., Conti, A., Sanvito, F., Innocenzi, A., Pecorelli, N., Braga, M., and Alessio, M.
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,autoantibodies ,Prognosi ,Colorectal cancer ,ADAM10 ,Disease ,Serology ,Immuno-proteomics ,ADAM10 Protein ,03 medical and health sciences ,Immune system ,Protein Domains ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Protein Precursors ,Autoantibodies ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Metalloproteinase ,business.industry ,Autoantibody ,Membrane Proteins ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Autoantibodie ,Immuno-proteomic ,Colorectal carcinoma ,030104 developmental biology ,immuno-proteomics ,Antibody Formation ,Immunology ,Female ,Clinical Research Paper ,Amyloid Precursor Protein Secretases ,Colorectal Neoplasms ,business ,ADAM10 metalloprotease - Abstract
A humoral immune response against aberrant tumor proteins can be elicited in cancer patients, resulting in the production of auto-antibodies (Abs). By serological proteome analysis we identified the surface membrane protein ADAM10, a metalloproteinase that has a role in epithelial-tumor progression and invasion, as a target of the immune response in colorectal cancer (Crc). A screening carried out on the purified protein using testing cohorts of sera (Crc patients n = 57; control subjects n = 39) and validation cohorts of sera (Crc patients n = 49; control subjects n = 52) indicated that anti-ADAM10 auto-Abs were significantly induced in a large group (74%) of colon cancer patients, in particular in patients at stage II and III of the disease. Interestingly, in Crc patients classified as stage III disease, the presence of anti-ADAM10 auto-Abs in the sera was associated with a favourable follow-up with a significant shifting of the recurrence-free survival median time from 23 to 55 months. Even though the ADAM10 protein was expressed in Crc regardless the presence of auto-Abs, the immature/non-functional isoform of ADAM10 was highly expressed in the tumor of anti-ADAM10-positive patients and was the isoform targeted by the auto-Abs. In conclusion, the presence of anti-ADAM10 auto-Abs seems to reflect the increased tumor expression of the immunogenic immature-ADAM10 in a group of Crc patients, and is associated with a favourable prognosis in patients at stage III of the disease.
- Published
- 2016
45. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct pre-vaccination gene expression profiles in blood
- Author
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Susan A. Doyle, Zhiquan Xiang, Larissa H. Haut, Raj K. Kurupati, S. Kannan, Hildegund C.J. Ertl, Yan Li, Andrew V. Kossenkov, Qin Liu, Kenneth E. Schmader, and Louise C. Showe
- Subjects
0301 basic medicine ,Male ,T-Lymphocytes ,medicine.disease_cause ,Antibodies, Viral ,Cohort Studies ,0302 clinical medicine ,Influenza A Virus, H1N1 Subtype ,Influenza A virus ,Ethnicity ,Medicine ,030212 general & internal medicine ,race ,Aged, 80 and over ,B-Lymphocytes ,biology ,Antibody titer ,Research Paper: Immunology ,Vaccination ,medicine.anatomical_structure ,Oncology ,Influenza Vaccines ,Immunology and Microbiology Section ,Female ,Antibody ,inactivated influenza vaccine ,Adult ,Influenza vaccine ,Black People ,Virus ,White People ,03 medical and health sciences ,Immunity ,Influenza, Human ,Humans ,Immune response ,B cell ,Aged ,B cell responses ,business.industry ,United States ,Black or African American ,030104 developmental biology ,Gene Expression Regulation ,Immunoglobulin M ,Vaccines, Inactivated ,Immunoglobulin G ,Immunology ,Antibody Formation ,biology.protein ,Leukocytes, Mononuclear ,business ,Transcriptome - Abstract
// Raj Kurupati 1,* , Andrew Kossenkov 1,* , Larissa Haut 1 , Senthil Kannan 1,2 , Zhiquan Xiang 1 , Yan Li 1 , Susan Doyle 3 , Qin Liu 1 , Kenneth Schmader 3 , Louise Showe 1 and Hildegund Ertl 1 1 The Wistar Institute, Philadelphia, PA, USA 2 Biomedical Graduate Group, University of Pennsylvania, Philadelphia, PA, USA 3 Development and Division of Geriatrics, GRECC, Durham VA Medical Center and Center for the Study of Aging and Human, Department of Medicine, Duke University Medical Center, Durham, NC, USA * These authors have contributed equally to this work Correspondence to: Hildegund Ertl, email: // Keywords : B cell responses, inactivated influenza vaccine, race, Immunology and Microbiology Section, Immune response, Immunity Received : June 17, 2016 Accepted : August 25, 2016 Published :August 30, 2016 Abstract We conducted a 5-year study analyzing antibody and B cell responses to the influenza A virus components of the inactivated influenza vaccine, trivalent (IIV3) or quadrivalent (IIV4) in younger (aged 35-45) and aged (≥65 years of age) Caucasian and African American individuals. Antibody titers to the two influenza A virus strains, distribution of circulating B cell subsets and the blood transcriptome were tested at baseline and after vaccination while expression of immunoregulatory markers on B cells were analyzed at baseline. African Americans mounted higher virus neutralizing and IgG antibody responses to the H1N1 component of IIV3 or 4 compared to Caucasians. African Americans had higher levels of circulating B cell subsets compared to Caucasians. Expression of two co-regulators, i.e., programmed death (PD)-1 and the B and T cell attenuator (BTLA) were differentially expressed in the two cohorts. Race-related differences were caused by samples from younger African Americans, while results obtained with samples of aged African Americans were similar to those of aged Caucasians. Gene expression profiling by Illumina arrays revealed highly significant differences in 1368 probes at baseline between Caucasians and African Americans although samples from both cohorts showed comparable changes in transcriptome following vaccination. Genes differently expressed between samples from African Americans and Caucasians regardless of age were enriched for myeloid genes, while the transcripts that differed in expression between younger African Americans and younger Caucasians were enriched for those specific for B-cells.
- Published
- 2016
46. Association of time since pneumococcal polysaccharide vaccine receipt and CD4 count with antibody response to the 13-valent pneumococcal conjugate vaccine in HIV-infected adults
- Author
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Tina D. Cunningham, Alexandria E.-B. Rossheim, Julia Siik, Anna Marie P. Young, and Stephanie B. Troy
- Subjects
Adult ,Male ,Time Factors ,030231 tropical medicine ,Immunology ,Enzyme-Linked Immunosorbent Assay ,HIV Infections ,complex mixtures ,Pneumococcal Infections ,Pneumococcal conjugate vaccine ,Pneumococcal Vaccines ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,030212 general & internal medicine ,Young adult ,Prospective cohort study ,Aged ,Pharmacology ,Receipt ,biology ,business.industry ,Middle Aged ,medicine.disease ,Pneumococcal polysaccharide vaccine ,Virology ,United States ,CD4 Lymphocyte Count ,Pneumococcal infections ,Antibody response ,Antibody Formation ,biology.protein ,Female ,Antibody ,business ,Research Paper ,medicine.drug - Abstract
Pneumococcal infection is a leading cause of illness and death in HIV-infected adults. Current United States guidelines for HIV-infected adults recommend a single dose of the 13-valent pneumococcal conjugate vaccine (PCV-13) at any CD4 count and at least 1 y after receipt of the 23-valent pneumococcal polysaccharide vaccine (PPV). PPV is known to lead to hyporesponsiveness to subsequent pneumococcal vaccines for at least 1 y Whether PCV-13 would be more immunogenic if administered later after PPV receipt or at higher CD4 counts has not been tested.We prospectively collected serum from 96 HIV-infected adults before and after PCV-13 receipt, and measured antibody concentrations against 4 pneumococcal serotypes (3, 6A, 7F, and 19A) via indirect ELISA according to the WHO protocol. Post-booster antibody concentrations and fold-rise in antibody concentrations were compared according to time from PPV receipt and baseline CD4 count using univariate and multivariate analyses.PPV receipt3 versus 1-3 y prior did not significantly change post-vaccination antibody concentrations, but was associated with slightly higher fold-rise in antibody concentration for the 3 tested serotypes included in PPV, though this only reached significance for serotype 7F. CD4 count was significantly associated with post-vaccination antibody concentrations for 3 of 4 serotypes, but not for fold-rise in antibody concentration for any serotype.Waiting longer than 1 y after PPV receipt to administer PCV-13 may slightly improve the antibody response to serotypes included in both vaccines. While higher CD4 count at PCV-13 administration results in higher post-vaccination antibody concentrations, this is likely because higher CD4 count is also associated with higher pre-vaccination antibody concentrations.
- Published
- 2016
47. The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection
- Author
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Hui-Mei Hu, Chien-Hsiung Pan, Hsin-Wei Chen, Chih-Hsiang Leng, Chun-Hsiang Hsieh, Han-Hsuan Chung, Pele Chong, Yu-Ju Hsiao, and Szu-Hsien Wu
- Subjects
0301 basic medicine ,T-Lymphocytes ,Immunology ,Dengue Vaccines ,Viremia ,Dengue virus ,Antibodies, Viral ,medicine.disease_cause ,Dengue fever ,Measles virus ,Interferon-gamma ,03 medical and health sciences ,Immunity ,Animals ,Immunology and Allergy ,Medicine ,Dengue vaccine ,Pharmacology ,Drug Carriers ,Vaccines, Synthetic ,biology ,business.industry ,Immunogenicity ,medicine.disease ,biology.organism_classification ,Research Papers ,Antibodies, Neutralizing ,Virology ,Mice, Inbred C57BL ,030104 developmental biology ,Antibody Formation ,biology.protein ,Antibody ,business - Abstract
Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 ≥ 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3-specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine.
- Published
- 2016
48. Assessment of immune responses to H5N1 inactivated influenza vaccine among individuals previously primed with H5N2 live attenuated influenza vaccine
- Author
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Igor Losev, Petukhova Gd, Alexandra Nikiforova, Marina Stukova, Donina Sa, Irina Isakova-Sivak, Anatoly Naykhin, Larisa Rudenko, Maureen Power, Mariana Erofeeva, Daniil Korenkov, and Jorge Flores
- Subjects
Adult ,Male ,safety ,Influenza vaccine ,Immunology ,Immunization, Secondary ,prime-boost strategy ,H5 avian influenza viruses ,live attenuated influenza vaccine ,Booster dose ,Cross Reactions ,Antibodies, Viral ,Vaccines, Attenuated ,medicine.disease_cause ,medicine ,Humans ,Immunology and Allergy ,Live attenuated influenza vaccine ,Pharmacology ,B-Lymphocytes ,Heterologous vaccine ,Influenza A Virus, H5N1 Subtype ,business.industry ,Immunogenicity ,Vaccination ,memory immune response ,Antibody titer ,clinical trial ,Hemagglutination Inhibition Tests ,Antibodies, Neutralizing ,Research Papers ,Virology ,Influenza A virus subtype H5N1 ,Immunoglobulin A ,Vaccines, Inactivated ,Influenza Vaccines ,Immunoglobulin G ,Antibody Formation ,Female ,Influenza A Virus, H5N2 Subtype ,business ,Immunologic Memory ,inactivated influenza vaccine - Abstract
During the past decade, a number of H5 subtype influenza vaccines have been developed and tested in clinical trials, but most of them induced poor serum antibody responses prompting the evaluation of novel vaccination approaches. One of the most promising ones is a "prime-boost" strategy, which could result in the induction of prompt and robust immune responses to a booster influenza vaccine following priming with homologous or heterologous vaccine strains. In our study we evaluated immunogenicity of an adjuvanted A(H5N1) inactivated influenza vaccine (IIV) in healthy adult subjects who received A(H5N2) live attenuated influenza vaccine (LAIV) 1.5 years earlier and compared this with a group of naïve subjects. We found that priming with A(H5N2) LAIV induced a long-lasting B-cell immunological memory against influenza A(H5N1) virus, which was brought on by more prompt and vigorous antibody production to a single dose of A(H5N1) IIV in the primed group, compared to the naïve controls. Thus, by day 28 after the first booster dose, the hemagglutination inhibition and neutralizing (MN) antibody titer rises were 17.2 and 30.8 in the primed group, compared to 2.3 and 8.0 in the control group, respectively. The majority (79%) of the primed individuals achieved seroprotective MN antibody titers at 7 days after the first dose of the IIV. All LAIV-primed volunteers had MN titers ≥ 1:40 by Day 28 after one dose of IIV, whereas only 58% subjects from the naïve control group developed similar immune responses at this time point. The second A(H5N1) IIV dose did not increase the immune response in the LAIV-primed group, whereas 2 doses of IIV were required for naïve volunteers to develop significant immune responses. These findings were of special significance since Russian-based LAIV technology has been licensed to WHO, through whom the vaccine has been provided to vaccine manufacturers in India, China and Thailand - countries particularly vulnerable to a pandemic influenza. The results of our study will be useful to inform the development of vaccination strategies in these countries in the event of a pandemic.
- Published
- 2015
49. Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation
- Author
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Steno Sentinelli, Paola Sinibaldi-Vallebona, Chiara De Luca, Ilaria Sciamanna, Michele Gallucci, Gerald G. Schumann, Corrado Spadafora, Fiorella Guadagni, and Andreas Hoffmann
- Subjects
0301 basic medicine ,Male ,Pathology ,Somatic cell ,Fluorescent Antibody Technique ,Cell Transformation ,medicine.disease_cause ,Immunoenzyme Techniques ,Mice ,Prostate ,Monoclonal ,Tumor Cells, Cultured ,Inbred BALB C ,Prostatic Intraepithelial Neoplasia ,Intraepithelial neoplasia ,Mice, Inbred BALB C ,Tumor ,Cultured ,Blotting ,Antibodies, Monoclonal ,RNA-Directed DNA Polymerase ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Prognosis ,Tumor Cells ,ORF2 ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Oncology ,Colonic Neoplasms ,Adenocarcinoma ,LINE-1/L1 ,Western ,Research Paper ,Adenoma ,medicine.medical_specialty ,Blotting, Western ,Antibodies ,03 medical and health sciences ,reverse transcriptase ,medicine ,Biomarkers, Tumor ,Animals ,Deoxyribonuclease I ,Humans ,Neoplasm Staging ,Neoplastic ,business.industry ,Cell growth ,retrotransposon ,Cancer ,Prostatic Neoplasms ,medicine.disease ,Endonucleases ,Reverse transcriptase ,tumorigenesis ,030104 developmental biology ,Tissue Array Analysis ,Antibody Formation ,Cancer research ,Neoplasm Grading ,Carcinogenesis ,business ,Biomarkers - Abstract
LINE-1 (L1) retrotransposons are a source of endogenous reverse transcriptase (RT) activity, which is expressed as part of the L1-encoded ORF2 protein (L1-ORF2p). L1 elements are highly expressed in many cancer types but not in differentiated somatic tissues. We previously found that RT inhibition reduces cell proliferation and promote differentiation in neoplastic cells, indicating that high endogenous RT activity promote cancer growth. Here we investigate the expression of L1-ORF2p in several human types ocancer.We have developed a highly specific monoclonal antibody (mAb chA1-L1) raised against the endonuclease domain of L1-ORF2p as a tool to study ORF2p expression and localization in human cancer cell lines and staged bioptic tissues. We uncover new evidence for high levels of L1-ORF2p in transformed cell lines and staged epithelial cancer tissues (colon, prostate, lung and breast) while no or only basal ORF2p expression was detected in non-transformed cells. An in-depth analysis of colon and prostate cancer tissues shows ORF2p expression in pre-neoplastic stages, namely transitional mucosa and prostate intraepithelial neoplasia (PIN), respectively. Our results show that L1-ORF2p is overexpressed in tumor tissues and in pre-neoplastic colon and prostate tissues; this latter finding suggests that ORF2p could be considered as a potential early cancer diagnostic biomarker.
- Published
- 2015
50. Transcriptional and clonal characterization of B cell plasmablast diversity following primary and secondary natural DENV infection
- Author
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Damon Ellison, Stefan Fernandez, Michael K. McCracken, Tao Li, Kaitlin Victor, Richard G. Jarman, Ariadna Grinyo i Escuer, Mallorie E. Fouch, Gregory D. Gromowski, Methee Gomootsukavadee, Anuja Mathew, Benjamin J. Doranz, Alan L. Rothman, Stephen J. Thomas, Edgar Davidson, Benjamin Gabriel, Caitlin Kuklis, Jeffrey R. Currier, Hayden Siegfried, Wiriya Rutvisuttinunt, Heather Friberg, Jenny Liang, Timothy P. Endy, Adam T. Waickman, and Anon Srikiatkhachorn
- Subjects
Monoclonal antibody ,0301 basic medicine ,medicine.medical_specialty ,Research paper ,medicine.drug_class ,viruses ,Cell ,Immunoglobulins ,lcsh:Medicine ,Biology ,Plasmablast ,General Biochemistry, Genetics and Molecular Biology ,Dengue fever ,Dengue ,Single-cell RNA sequencing ,03 medical and health sciences ,0302 clinical medicine ,Medical microbiology ,medicine ,Humans ,RNA-Seq ,Cells, Cultured ,B cell ,B-Lymphocytes ,lcsh:R5-920 ,lcsh:R ,virus diseases ,RNA ,General Medicine ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Virology ,Immunity, Humoral ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Antibody Formation ,Humoral immunity ,Commentary ,biology.protein ,Single-Cell Analysis ,Antibody ,Transcriptome ,lcsh:Medicine (General) ,IgA - Abstract
Antibody-mediated humoral immunity is thought to play a central role in mediating the immunopathogenesis of acute DENV infection, but limited data are available on the diversity, specificity, and functionality of the antibody response at the molecular level elicited by primary or secondary DENV infection. In order to close this functional gap in our understanding of DENV-specific humoral immunity, we utilized high-throughput single cell RNA sequencing to investigate B cells circulating in both primary and secondary natural DENV infections. We captured full-length paired immunoglobulin receptor sequence data from 9,027 B cells from a total of 6 subjects, including 2,717 plasmablasts. In addition to IgG and IgM class-switched cells, we unexpectedly found a high proportion of the DENV-elicited plasmablasts expressing IgA, principally in individuals with primary DENV infections. These IgA class-switched cells were extensively hypermutated even in individuals with a serologically confirmed primary DENV infection. Utilizing a combination of conventional biochemical assays and high-throughput shotgun mutagenesis, we determined that DENV-reactive IgA class-switched antibodies represent a significant fraction of DENV-reactive Igs generated in response to DENV infection, and that they exhibit a comparable epitope specificity to DENV-reactive IgG antibodies. These results provide insight into the molecular-level diversity of DENV-elicited humoral immunity and identify a heretofore unappreciated IgA plasmablast response to DENV infection. Keywords: Dengue, Plasmablast, Single-cell RNA sequencing, IgA, Monoclonal antibody
- Published
- 2020
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