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Veterinary drug residues in food-producing animals pose a threat to human health and public safety, and accurate measurement of these drug residues is necessary. However, detecting nitrofuran metabolite residues is challenging because of their low molecular weight and the long derivatisation time required for their indirect detection. Current antibodies produced against these metabolites have limited accuracy and sensitivity owing to the traditional and ineffective hapten design based on the reaction of 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ) with nitrobenzaldehyde. In this study, a new antigen strategy was adopted using an original-structure-based hapten design combined with a new carrier protein with immunosynergistic effects to produce a monoclonal antibody that could recognise the metabolite of furaltadone (AMOZ) directly without derivatisation with excellent analytical performance. Finally, a gold-based paper lateral flow immunoassay for AMOZ without derivatisation was established with a visual limit of detection of 5 ng/mL, IC 50 of 0.97 ng/mL and linear range (IC 20 ∼IC 80) of 0.45–2.07 ng/mL. The method was sensitive and accurate, and detection was completed within 10 min. This new antigen design strategy provides a theoretical basis and reference for antibody production of other ultrasmall molecules. [Display omitted] • An antigen strategy of AMOZ was proposed by hapten design and new carrier proteins. • The excellent antibody directly recognizes AMOZ without derivatization. • Effect of EP distribution and spatial structure to antibody production was studied. • This method could be used as a rapid screening method for AMOZ analysis on site. [ABSTRACT FROM AUTHOR]

Measurement of anti-pneumococcal capsular polysaccharides (anti-PnPs) IgG titers is an important tool in the immunologic assessment of patients with suspected immunodeficiency disorders (ID) to reduce the morbi-mortality and minimize severe infections. Retrospectively, we studied the relationship among anti-PnPs IgG response to 3 doses of Prevenar®13, levels of immune system components, leukocyte populations, and clinical data in children with ID. Serum samples were collected at least 4 weeks post vaccination. Subsequently, multi-serotype enzyme-linked immunosorbent assay (ELISA) was performed. Eighty-seven children (under 12 years) were enrolled. Primary immunodeficiency disorder (PID) was the most common disorder (45) followed by possible immunodeficiency disorder (POID) (19), secondary immunodeficiency disorder (SID) (15), and mixed immunodeficiency disorder (MID) (8). The median age was 3 (1.50-5.33) years, 65% of patients were male. Deficient production of anti-PnPs IgG (titer ≤ 50 mg/L) was detected in 47 patients (54%), especially in the MID group, all of them under immunosuppressive therapy. In PCV13 responders, the mean of leukocyte population levels was higher with statistically significance differences in CD4 + /CD8 + T lymphocytes (p = 0.372, p = 0.014) and CD56 + /CD16 + NK (p = 0.016). Patients with previous bone marrow transplantation were the worst PCV13 responders. Pneumococcal IgG antibody titers (post-vaccination) along with clinical and analytical markers represented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 (IC50) 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]

Furthermore, it has been reported that MS patients using anti-CD20 therapy have suppressed antibody response to infection with the novel coronavirus (SARS-CoV-2) and to some vaccines (not against COVID-19) [[1], [3]-[5]]. Dear Sirs, We read with great interest the paper by Khayat Khoei et al. which presented negative anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) antibody response after Pfizer SARS-CoV-2 vaccination in a patient with relapsing-remitting multiple sclerosis (RRMS) on ocrelizumab [[1]]. [Extracted from the article]

• An immunosensor was developed for the determination of amanitins. • Half-maximal inhibitory concentration was 0.48 ng/mL and the LOD was 0.095 ng/mL. • Good correlations of the results verified by immunosensor and LC–MS/MS. Amanitin (AMA) is responsible for human fatalities after ingestion of poisonous mushrooms, thus, a rapid and accurate detection method is urgently needed. Here, gold nanoparticle-based immunosensor with monoclonal antibody against AMA was constructed for rapid detection of alpha- and beta-amanitin (α- and β-AMA) in mushroom, serum and urine samples. Under optimized conditions, the visual limits of detection (vLOD) and calculated LOD for α-AMA and β-AMA in mushroom were 10 ng/g, 20 ng/g, and 0.1 ng/g, 0.2 ng/g, respectively. Analysis of wild mushroom samples was also performed using a strip scan reader in the 10 min range. Furthermore, in mushrooms containing amatoxins results were confirmed and compared with those determined by liquid chromatography tandem mass spectrometry. Thus, this immunosensor provided a useful monitoring tool for rapid detection and screening of mushroom samples and in serum and urine from subjects who accidentally consumed AMA-containing mushrooms. [ABSTRACT FROM AUTHOR]

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]

Objective: Psychological distress has been associated with dampened antibody production following vaccination. Questions remain, however, about whether psychological distress influences vaccine response uniformly across the lifespan, and whether changes in distress result in changes in antibody production across the same period., Methods: Participants (N = 148; M age  = 32.2 years, SD = 19.7, range = 12-80 years) took part in consecutive vaccine studies during the 2017-2018 and 2018-2019 influenza seasons. Each influenza season, they reported on their depressive symptoms, provided blood samples, and received the standard influenza vaccine. Participants then provided a second blood sample one month later. Antibody titers were examined pre- and post-vaccination., Results: Analyses examined both within-season and across-season effects of depressive symptoms, age, and their interaction on vaccine response. Within-season analyses revealed that age predicted antibody response during both seasons (2017-2018 and 2018-2019). Neither depressive symptoms nor the interaction with age were associated with antibody response to vaccination within either season. Across the two seasons, age significantly moderated the association between change in depressive symptoms and change in antibody production. For people who were 48 or older, increases in depressive symptoms across the two seasons were associated with a less robust response to the vaccine in the second season relative to the first season. For people younger than 48, changes in depressive symptoms were not significantly related to changes in antibody production., Conclusions: These findings highlight the important role of mental health for older adults' vaccine response, which could have clinical relevance for protection against disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

An issue with many current vaccines is the dependency on broadly inflammatory adjuvants, such as aluminum hydroxide or aluminum salts that affect many immune- and non-immune cells. These adjuvants are not necessarily activating all antigen-presenting cells (APCs) that take up the antigen and most likely they also activate APCs with no antigen uptake, as well as many non-immune cells. Conjugation of antigen and adjuvant would enable the use of smaller amounts of adjuvant and avoid unnecessary tissue damage and activation of bystander cells. It would ensure that all APCs that take up the antigen would also become activated and avoid that immature and non-activated APCs present the antigen to T cells without a co-stimulatory signal, leading to tolerogenesis. We have developed a novel vaccine that co-deliver antigen and a nucleotide adjuvant to the same APC and lead to a strong activation response in dendritic cells and macrophages. The vaccine is constructed as a fusion-protein with an antigen fused to the DNA/RNA-binding domain from the Hc2 protein from Chlamydia trachomatis. We have found that the fusion protein is able to package polyinosinic:polycytidylic acid (poly(I:C)) or dsDNA into small particles. These particles were taken up by macrophages and dendritic cells and led to strong activation and maturation of these cells. Immunization of mice with the fusion protein packaged poly(I:C) led to a stronger antibody response compared to immunization with a combination of poly(I:C) and antigen without the Hc2 DNA/RNA-binding domain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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]

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]

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]

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]

The 3-dose COVID-19 vaccine (booster vaccination) has been offered worldwide. As booster vaccinations continue, it is important to understand the antibody dynamics elicited by booster vaccination in order to evaluate and develop vaccination needs and strategies. Here, we investigated longitudinal data by monitoring IgG antibodies against the receptor binding domain (RBD) in health care workers. We extended our previously developed mathematical model to booster vaccines and successfully fitted antibody titers over time in the absence and presence of past SARS-CoV-2 infection. Quantitative analysis using our mathematical model indicated that anti-RBD IgG titers increase to a comparable extent after booster vaccination, regardless of the presence or absence of infection, but infection history extends the duration of antibody response by 1.28 times. Such a mathematical modeling approach can be used to inform future vaccination strategies on the basis of an individual's immune history. Our simple quantitative approach can be extended to any kind of vaccination and therefore can form a basis for policy decisions regarding the distribution of booster vaccines to strengthen immunity in future pandemics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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]

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]

Background: Humoral response against SARS-CoV-2 is increasingly accepted as the central correlate of immune protection. Recent pediatric seroprevalence data are extremely limited. Significant knowledge gaps also exist in immune response to mRNA SARS-CoV-2 vaccination in children. As children demonstrate distinct response to naïve infection relative to adults, it is essential to investigate age-specific differences in seroprevalence and antibody response to SARS-CoV-2 vaccination., Methods: Seroprevalence was assessed through two cross-sectional serosurveys prior to COVID-19 vaccination approval in children <5 years using residual patient specimens (n = 2902). To assess antibody response post-vaccination, 842 participants (580 children, 262 adults) were prospectively recruited with informed consent. Participation required completion of a health questionnaire and blood donation. Samples were collected at varying times post-vaccination and assayed using the Abbott AdviseDx SARS-CoV-2 IgG II and DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assays., Results: Significant increases in seroprevalence were observed between the first and second serosurveys in unvaccinated children <6 months to 5 years (38-75%). In the prospective vaccination cohort, serokinetic response decreased with time post-dose of an mRNA vaccine. Measured IgG titres were significantly higher in children relative to adults across all time points., Conclusions: This is the largest evaluation of quantitative SARS-CoV-2 antibody assays in a cohort of Canadian children, adolescents, and adults. Findings suggest high rates of SARS-CoV-2 exposure among unvaccinated young children in the Toronto community. Additional data supports children have higher antibody titres relative to adults post-vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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]

Background: Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models., Materials: PubMed and Web of Science databases were used to identify eligible papers published until May 2022. Eligible publications included those studying mathematical models that measure antibody kinetics as the primary outcome (ranging from phenomenological to mechanistic models)., Results: We identified 78 eligible publications, of which 8 relied on an Ordinary Differential Equations (ODEs)-based modelling approach to describe antibody kinetics after vaccination, and 12 studies used such models in the context of humoral immunity induced by natural infection. Mechanistic modeling studies were summarized in terms of type of study, sample size, measurements collected, antibody half-life, compartments and parameters included, inferential or analytical method, and model selection., Conclusions: Despite the importance of investigating antibody kinetics and underlying mechanisms of (waning of) the humoral immunity, few publications explicitly account for this in a mathematical model. In particular, most research focuses on phenomenological rather than mechanistic models. The limited information on the age groups or other risk factors that might impact antibody kinetics, as well as a lack of experimental or observational data remain important concerns regarding the interpretation of mathematical modeling results. We reviewed the similarities between the kinetics following vaccination and infection, emphasising that it may be worth translating some features from one setting to another. However, we also stress that some biological mechanisms need to be distinguished. We found that data-driven mechanistic models tend to be more simplistic, and theory-driven approaches lack representative data to validate model results., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Irene Garcia-Fogeda reports financial support was provided by University of Antwerp. Niel Hens (NH) reports that the Universities of Antwerp and Hasselt have received funding for advisory boards and research projects of MSD, GSK, JnJ, Pfizer outside the proposed work. NH did not receive any personal remuneration., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This paper presents two viral infection models that describe dynamics of the virus under the effect of two distinct types of antibodies. The first model considers the population of five compartments, target cells, infected cells, free virus particles, antibodies type-1 and antibodies type-2. The presence of two types of antibodies can be a result of secondary viral infection. In the second model, we incorporate the latently infected cells. We assume that the antibody responsiveness is given by a combination of the self-regulating antibody response and the predator–prey-like antibody response. For both models, we verify the nonnegativity and boundedness of their solutions, then we outline all possible equilibria and prove the global stability by constructing proper Lyapunov functions. The stability of the uninfected equilibrium EQ 0 and infected equilibrium EQ * is determined by the basic reproduction number R 0 . The theoretical findings are verified through numerical simulations. According to the outcomes, the trajectories of the solutions approach EQ 0 and EQ * when R 0 ≤ 1 and R 0 > 1 , respectively. We study the sensitivity analysis to show how the values of all the parameters of the suggested model affect R 0 under the given data. The impact of including the self-regulating antibody response and latently infected cells in the viral infection model is discussed. We showed that the presence of the self-regulating antibody response reduces R 0 and makes the system more stabilizable around EQ 0 . Moreover, we established that neglecting the latently infected cells in the viral infection modeling leads to the design of an overflow of antiviral drug therapy. [ABSTRACT FROM AUTHOR]

Antibodies against small molecules with high titer and high affinity are always pursued in the field of vaccines for drugs of abuse, antidotes to toxins and immunoassays in medical, environmental, and food safety. The exposure degree of the target molecule to the immune system is critical to induce a strongly specific antibody response, thus, the spacer arm length between the target molecule and carrier protein plays an important role. However, the influence of spacer arm length on antibody titer, affinity, and assay performance is not yet clear and highly demanded to be addressed. In the present study, we proposed a model study to answer the question by using two typical small molecules, melamine and p-nitroaniline, which were introduced by varied spacer arms with increasing alkane linear length from 2 to 12 carbon atoms brick by brick. The spacer arm lengths of the haptens were obtained by computational chemistry. The titer and affinity of mouse antisera were analyzed and compared, showing that all haptens with spacer arms of 6-8 carbon atoms, i.e. 6.3-8.8 Å in length, induced strong antibodies represented by the highest titer and affinity without exception, while the haptens with spacer arms of 2-4 carbon atoms and 10-12 carbon atoms, i.e. 1.5-3.9 Å and 11.3-13.9 Å in length, failed to induce high-quality antibody response. Moreover, the titer and sensitivity of the subsequently developed immunoassays were significantly affected by using coating haptens with different spacer arm lengths, and coating haptens with a spacer arm of 6.3-8.8 Å in length delivered the optimum detection performance. The antibody recognition mechanism study further confirmed that the hapten spacer arm length had a critical effect on the recognition properties of the induced antibody, which should be interactive with the spacer arm each other. This study showed that the hapten with appropriate spacer arm length is important to antibody response and immunoassay development, providing a valuable and general clue for the rational design of hapten., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Several studies have shown that intradermal vaccination leads to improved immune responses. In addition, lowering vaccine doses will reduce costs and therefore potentially increase coverage. To determine whether intradermal delivery enhances the antibody responses against the 13-valent pneumococcal conjugate vaccine (PCV13), we compared intradermally and intramuscularly vaccinated mice., Methods: Mice were immunized with PCV13, either intradermally or intramuscularly and CFU-counts in the nasal tissue were determined three or seven days after intranasal colonization with a serotype 4 clinical strain. Antibody concentrations against all thirteen polysaccharides were measured in blood and mucosal samples using a fluorescent-bead-based multiplex immunoassay., Results: Antibody levels in both serum and mucosal samples were higher in the intramuscularly vaccinated group as compared to the intradermally vaccinated group. No protection against S. pneumoniae intranasal colonization was observed for either vaccination route., Conclusions: Intradermal vaccination was inferior to intramuscular immunization in inducing serotype-specific antibodies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The emergence of the covid19 pandemic has forced many countries to be more focused on the technologies that can save human life. A lot of efforts have focused on containment and mitigation actions with varying degrees of success. However, lack of attention given to administering urgent requests for convalescent plasma blood as part of treatment for critical covid19 patients although the passive administration of antibodies from a person who has convalesced may be an effective therapy for those patients who have yet to develop their antibody response. Hence, interest in the use of convalescent plasma has been rising, not only commenced by medical professionals but also among patients' family members, especially for urgent requests. This paper proposed timelinebased posts to tackle the urgent-request issue that sort based on first come first serve priority. From this timeline, the people in search of donors may find donors' information and location quickly. Furthermore, we added a timeline page, search function, a virtual assistant (chatbot) that automatically shares posts to social media without exiting the app, etc. These features promote the hit to the right users and their respond faster than before. The previous study reported from the 40 PSARS patients undergoing ribavirin and methylprednisolone treatment, 19 were administered with convalescent plasma, whereas 21 were given an additional dose of methylprednisolone. The group of patients who were treated with plasma therapy showed better recovery and reduced mortality. With this situation, we hope our contribution in the form of an Android app can assist those in need at the right time and save more lives. Moreover, this app can be referred to as a model for other comparable apps. [ABSTRACT FROM AUTHOR]

This paper develops a mathematical model to investigate the Human Immunodeficiency Virus (HIV) infection dynamics. The model includes two transmission modes (cell-to-cell and cell-free), two adaptive immune responses (cytotoxic T-lymphocyte (CTL) and antibody), a saturated CTL immune response, and latent HIV infection. The existence and local stability of equilibria are fully characterized by four reproduction numbers. Through sensitivity analyses, we assess the partial rank correlation coefficients of these reproduction numbers and identify that the infection rate via cell-to-cell transmission, the number of new viruses produced by each infected cell during its life cycle, the clearance rate of free virions, and immune parameters have the greatest impact on the reproduction numbers. Additionally, we compare the effects of immune stimulation and cell-to-cell spread on the model's dynamics. The findings highlight the significance of adaptive immune responses in increasing the population of uninfected cells and reducing the numbers of latent cells, infected cells, and viruses. Furthermore, cell-to-cell transmission is identified as a facilitator of HIV transmission. The analytical and numerical results presented in this study contribute to a better understanding of HIV dynamics and can potentially aid in improving HIV management strategies. [ABSTRACT FROM AUTHOR]

The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse. [ABSTRACT FROM AUTHOR]

This paper aimed to investigate the influence of polymorphisms in the FCGR2A gene encoding R131H FcgRIIA variants and in the FCGR3B gene (108G > C, 114C > T, 194 A > G, 233C > A, 244 G > A and 316G > A) encoding FcgRIIIB-NA1, -NA2 and -SH variants on malaria susceptibility and antibody responses against P. falciparum merozoite antigens in Beninese children. An active malaria follow-up was conducted in infants from birth to 24 months of age in Allada, Benin. FCGR3B exon 3 was sequenced and FCGR2A exon 4 was genotyped. Antibodies directed to GLURP and MSP3 were quantified by ELISA. Association studies were performed using mixed-effect models. Individual carriage of FCGR3B 194 AA genotype was associated with a high number of malaria infections and a low level of IgG1 against MSP3 and GLURP-R0. High parasitemia and increased malaria infections were observed in infants carrying the FCGR3B*05 108C-114T-194A-233C-244A-316A haplotype. A reduced risk of malaria infections and low parasitemia were related to the carriages of the FCGR3B 108C-114T-194G-233C-244G-316A (FCGR3B*06), FCGR3B 108C–114T–194G–233A–244A–316A (FCGR3B*03 encoding for FcgRIIIB-SH) haplotypes and FCGR3B 297 TT genotype. Our results highlight the impact of FCGR3B polymorphisms on the individual susceptibility to malaria and antibody responses against MSP3 and GLURP in Beninese children. [ABSTRACT FROM AUTHOR]

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that have become fixed in the human genome. While HERV genes are typically silenced in healthy somatic cells, there are numerous reports of HERV transcription and translation across a wide spectrum of cancers, while T and B cell responses against HERV proteins have been detected in cancer patients. This review systematically categorizes the published evidence on the expression of and adaptive immune response against specific HERVs in distinct cancer types. A systematic literature search was performed using Medical Search Headings (MeSH) in the PubMed/Medline database. Papers were included if they described the translational activity of HERVs. We present multiple tables that pair the protein expression of specific HERVs and cancer types with information on the quality of the evidence. We find that HERV-K is the most investigated HERV. HERV-W (syncytin-1) is the second-most investigated, while other HERVs have received less attention. From a therapeutic perspective, HERV-K and HERV-E are the only HERVs with experimental demonstration of effective targeted therapies, but unspecific approaches using antiviral and demethylating agents in combination with chemo- and immunotherapies have also been investigated.

Pneumococcal conjugate vaccines reduce pneumococcal colonization via serotype-specific immunoglobulin G (IgG) at mucosal surfaces. The infant immunization schedule with the ten-valent pneumococcal conjugate vaccine (PCV10) changed from a 3 + 1 schedule (2-3-4-11 months) to a 2 + 1 schedule (2-4-11 months) in The Netherlands in 2013. We compared anti-pneumococcal IgG concentrations in saliva between the schedules. IgG was measured using a fluorescent bead-based multiplex immunoassay at the ages of 6 (post-primary) and 12 (post-booster) months in 51 infants receiving the 3 + 1 schedule and 68 infants receiving the 2 + 1 schedule. Post-primary IgG geometric mean concentrations (GMCs) were comparable between schedules for all vaccine serotypes. Post-booster IgG GMCs were significantly lower after the 2 + 1 schedule for serotypes 4 (p = 0.035), 7F (p = 0.048) and 23F (p = 0.0056). This study shows small differences in mucosal IgG responses between a 3 + 1 and a 2 + 1 PCV10 schedule. Future studies should establish correlates of protection against pneumococcal colonization for mucosal antibodies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

SARS-CoV-2 infection causes diverse outcomes ranging from asymptomatic infection to respiratory distress and death. A major unresolved question is whether prior immunity to endemic, human common cold coronaviruses (hCCCoVs) impacts susceptibility to SARS-CoV-2 infection or immunity following infection and vaccination. Therefore, we analyzed samples from the same individuals before and after SARS-CoV-2 infection or vaccination. We found hCCCoV antibody levels increase after SARS-CoV-2 exposure, demonstrating cross-reactivity. However, a case-control study indicates that baseline hCCCoV antibody levels are not associated with protection against SARS-CoV-2 infection. Rather, higher magnitudes of pre-existing betacoronavirus antibodies correlate with more SARS-CoV-2 antibodies following infection, an indicator of greater disease severity. Additionally, immunization with hCCCoV spike proteins before SARS-CoV-2 immunization impedes the generation of SARS-CoV-2-neutralizing antibodies in mice. Together, these data suggest that pre-existing hCCCoV antibodies hinder SARS-CoV-2 antibody-based immunity following infection and provide insight on how pre-existing coronavirus immunity impacts SARS-CoV-2 infection, which is critical considering emerging variants., Competing Interests: Declaration of interests P.G.T. has consulted for Illumina and 10X and serves on the advisory board of Immunoscape and Cyotagents. P.G.T. and J.C.C. filed patents related to treatment of severe respiratory infections, including SARS-CoV-2 (not based on research in this paper)., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

BACKGROUND Monoclonal antibodies (mAbs) presently dominate the biotherapeutic market. However, biotherapeutics in general, and mAbs in particular, are expensive therapies and outside the realm of affordability for most of the world. In an attempt to lower their cost of manufacturing, a novel in‐house non‐protein A continuous platform has recently been reported for mAb purification. In this paper, we perform an in‐depth evaluation of the process economics to assess the impact of removing the protein A step on the cost of goods (COGs). RESULTS: The non‐protein A platform was found to result in significant savings in COGs at about 23% when comparing both platforms in batch mode. Conversion of the non‐protein A platform from batch to continuous mode led to a further increase in these savings with about 39% gains in COGs over the conventional protein A platform. CONCLUSIONS: The non‐protein A purification platform offers a viable alternative to the standard protein A platform and can be considered when setting up a new facility. The continuous non‐protein A platform can especially be considered given the flexibility of the setup and the utility at both small and large scales. © 2021 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Objectives: The aim of this paper was to investigate the impact of different variables on the production of antibodies in patients who were infected with Covid-19. Methods: This cross-sectional study was conducted in Duhok City, Kurdistan Region of Iraq. The study was conducted between January 2021 and March 2022. Demographic data were collected via face-to-face interview. Antibody levels were determined using Elecsys Anti-SARS-CoV-2. Results: The levels of antibody were studied in 138 patients. A significant association was found between antibody levels and the age of the participants (r = 0.175; P = 0.04). Besides, a significant correlation was found between antibody levels and the duration of symptoms (r = 0.206; P = 0.015). The antibody levels were not associated with gender; history of chronic diseases; marital status or time interval before testing. Conclusion: Different variables that may impact the levels of antibody were studied. Significant associations were found between antibody levels and both age and duration of symptoms. Our results can be used by healthcare providers to focus on patients who are at risk of low antibody production. [ABSTRACT FROM AUTHOR]

This review article concerns the production of recombinant antibody fragments for applications mainly in the diagnostic sector. The so-called "point of care diagnostics" is very important for timely diagnosis and treatment, thus being able to save lives and resources. There is intense pressure for more accurate and less expensive rapid diagnostic tests, with a value preferably <$1. Thus, the large-scale cost-effective production of recombinant antibodies is vital. The importance of Escherichia coli toward the production of inexpensive rapid tests will be explained in this review paper. Details about the different strains of E. coli, the strategies used for the insertion and the expression of recombinant proteins, and the challenges that still exist are provided. Afterward, the importance of the expression scale and culture parameters in the final yield of the antibodies are examined. From this analysis, it appears that for good yields of recombinant antibodies, aside from appropriate gene transfer and expression, the culturing parameters are of paramount importance. Larger scale production is more favorable, mainly due to the higher cell densities that can be achieved. Yields of functional Fab fragments in the range of 10–20 mg/L are considered good in shake flasks, whereas in bioreactors can be up to 1–2 g/L. An amount of 10–500 mg of such antibody per million rapid tests is required. Despite the substantial importance of the production of the antibodies and their fragments, their downstream processing should be appropriately considered from the beginning for achieving the target value of the final rapid diagnostic tests. [ABSTRACT FROM AUTHOR]

Several patients with myasthenia gravis (MG) do not adequately respond to available drugs or exhibit poor tolerance, necessitating the need for new therapies. The paper discusses the rapidly evolving target-specific immunotherapies that promise long-standing remissions in the management of MG. It is specifically focused on the role of complement, anti-complement therapeutics, and the anti-FcRn and B cell monoclonals. Anti-AChR antibodies cause internalization of the receptors and activate complement leading to in situ MAC formation that damages the post-synaptic membrane of the neuromuscular junction. Inhibiting MAC formation by antibodies targeting key complements subcomponents is a reasonable therapeutic goal. Indeed, the anti-C5 monoclonal antibodies, Eculizumab, Ravulizumab, and Zilucoplan, have been successfully tested in MG with Eculizumab first and now Ravulizumab FDA-approved for refractory MG based on sustained long-term benefits. Among the biologics that inhibit FcRn, Efgartigimod caused rapid reduction of the circulating IgG in the lysosomes, and induced sustained clinical remission with good safety profile leading to FDA-approved indication. Anti-B cell agents, like Rituximab, can induce sustained long-term remissions, especially in IgG4 antibody-mediated Musk-MG, by targeting short-lived antibody-secreting plasmablasts. These biologics offer effective targeted immunotherapies with good tolerance promising to change the therapeutic algorithm in the chronic MG management. [ABSTRACT FROM AUTHOR]

Background: Following a relatively mild first wave of coronavirus disease 2019 (COVID-19) in India, a deadly second wave of the pandemic overwhelmed the healthcare system due to the emergence of fast-transmitting SARS-CoV-2 genetic variants. The emergence and spread of the B.1.617.2/Delta variant considered to be driving the devastating second wave of COVID-19 in India. Currently, the Delta variant has rapidly overtaken the previously circulating variants to become the dominant strain. Critical mutations in the spike/RBD region of these variants have raised serious concerns about the virus's increased transmissibility and decreased vaccine effectiveness. As a result, significant scientific and public concern has been expressed about the impact of virus variants on COVID-19 vaccines., Objectives: The purpose of this article is to provide an additional explanation in the context of the evolutionary trajectory of SARS-CoV-2 variants in India, the vaccine-induced immune response to the variants of concern (VOC), and various vaccine deployment strategies to rapidly increase population immunity., Content: Phylogenetic analysis of SARS-CoV-2 isolates circulating in India suggests the emergence and spread of B.1.617 variant. The immunogenicity of currently approved vaccines indicates that the majority of vaccines elicit an antibody response and some level of protection. According to current data, vaccines in the pre-fusion configuration (2p substitution) have an advantage in terms of nAb titer, but the duration of vaccine-induced immunity, as well as the role of T cells and memory B cells in protection, remain unknown. Since vaccine efficacy on virus variants is one of the major factors to be considered for achieving herd immunity, existing vaccines need to be improved or effective next-generation vaccines should be developed to cover the new variants of the virus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

The SARS-CoV-2 vaccination campaign began in February 2021 and achieved a high rate of 62.7% of the total population fully vaccinated by August 16, 2021, in Mongolia. We aimed to assess the initial protective antibody production after two doses of a variety of types of SARS-CoV-2 vaccines in the Mongolian pre-vaccine antibody-naïve adult population. This prospective study was conducted from March-April to July-August of 2021. All participants received one of the four government-proposed COVID-19 vaccines including Pfizer/BioNTech (BNT162b2), AstraZeneca (ChAdOx1-S), Sinopharm (BBIBP-CorV), and Sputnik V (Gam-COVID-Vac). Before receiving the first shot, anti-SARS-CoV-2 S-RBD human IgG titers were measured in all participants (n = 1833), and titers were measured 21–28 days after the second shot in a subset of participants (n = 831). We found an overall average protective antibody response of 84.8% (705 of 831 vaccinated) in 21–28 days after two doses of the four types of COVID-19 vaccines. Seropositivity and titer of protective antibodies produced after two shots of vaccine were associated with the vaccine types, age, and residence of vaccinees. Seropositivity rate varied significantly between vaccine types, 80.0% (28 of 35) for AstraZeneca ChAdOx1-S; 97.0% (193 of 199) for Pfizer BNT162b2; 80.7% (474 of 587) for Sinopharm BBIBP-CorV, and 100.0% (10 of 10) for Sputnik V Gam-COVID-Vac, respectively. Immunocompromised vaccinees with increased risk for developing severe COVID-19 disease had received the Pfizer vaccine and demonstrated a high rate of seropositivity. A high geometric mean titer (GMT) was found in vaccinees who received BNT162b2, while vaccinees who received ChAdOx1-S, Sputnik V, and BBIBP-CorV showed a lower GMT. In summary, we observed first stages of the immunization campaign against COVID-19 in Mongolia have been completed successfully, with a high immunogenicity level achieved among the population with an increased risk for developing severe illness. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs), crucial in medicine and biopharmaceuticals, require optimized large-scale production to meet high clinical dosage demands. Most of the processes for industrial mAb production rely on fed-batch operations, resulting in significant downtime. Transitioning to fully continuous and integrated processes holds the potential to boost product yield, enhance quality, and reduce storage costs for intermediate products. The integrated continuous mAb production process can be divided into the upstream and downstream processes. One crucial aspect that ensures the continuity of the integrated process is the switching of the capture columns, which are typically chromatography columns operated in a fed-batch manner downstream. Due to the discrete nature of the switching operation, advanced process control algorithms such as economic MPC (EMPC) are computationally difficult to implement. This is because an integer nonlinear program (INLP) needs to be solved online at each sampling time. This paper introduces two computationally-efficient approaches for EMPC implementation, namely, a sigmoid function approximation approach and a rectified linear unit (ReLU) approximation approach. It also explores the application of deep reinforcement learning (DRL). These three methods are compared to the traditional switching approach which is based on a 1 % product breakthrough rule and which involves no optimization. • An optimal control formulation for the switching operation in mAb production. • Two approximation methods for solving the optimal control problem. • Extensive simulation results showing the properties of the solving methods. [ABSTRACT FROM AUTHOR]

Patients with severely impaired antibody responses represent a group at-risk in the SARS-CoV-2 pandemic due to the lack of Spike-specific neutralizing antibodies. The main objective of this paper was to assess, by a longitudinal prospective study, COVID-19 infection and mortality rates, and disease severity in the first two years of the pandemic in a cohort of 471 Primary Antibody Defects adult patients. As secondary endpoints, we compared SARS-CoV-2 annual mortality rate to that observed over a 10-year follow-up in the same cohort, and we assessed the impact of interventions done in the second year, vaccination and anti-SARS-CoV-2 monoclonal antibodies administration on the disease outcome. Forty-one and 84 patients were infected during the first and the second year, respectively. Despite a higher infection and reinfection rate, and a higher COVID-19-related mortality rate compared to the Italian population, the pandemic did not modify the annual mortality rate for any cause in our cohort compared to that registered over the last ten years in the same cohort. PADs patients who died from COVID-19 had an underlying end-stage lung disease. We showed a beneficial effect of MoAbs administration on the likelihood of hospitalization and development of severe disease. In conclusion, COVID-19 did not cause excess mortality in Severe Antibody Deficiencies. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 enters the body through inhalation or self-inoculation to mucosal surfaces. The kinetics of the ocular and nasal mucosal-specific-immunoglobulin A(IgA) responses remain under-studied. Methods: Conjunctival fluid (CF, n = 140) and nasal epithelial lining fluid (NELF, n = 424) obtained by paper strips and plasma (n = 153) were collected longitudinally from SARS-CoV-2 paediatric (n = 34) and adult (n = 47) patients. The SARS-CoV-2 spike protein 1(S1)-specific mucosal antibody levels in COVID-19 patients, from hospital admission to six months post-diagnosis, were assessed. Results: The mucosal antibody was IgA-predominant. In the NELF of asymptomatic paediatric patients, S1-specific IgA was induced as early as the first four days post-diagnosis. Their plasma S1-specific IgG levels were higher than in symptomatic patients in the second week after diagnosis. The IgA and IgG levels correlated positively with the surrogate neutralization readout. The detectable NELF "receptor-blocking" S1-specific IgA in the first week after diagnosis correlated with a rapid decline in viral load. Conclusions: Early and intense nasal S1-specific IgA levels link to a rapid decrease in viral load. Our results provide insights into the role of mucosal immunity in SARS-CoV-2 exposure and protection. There may be a role of NELF IgA in the screening and diagnosis of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Pluronic F-68 is a nonionic surfactant, which is often used in the upstream process of biopharmaceutical production. However, the number of analytical methods developed for determination of Pluronic F-68 in the in-process and drug substance samples of biological drug production process is quite low. The lack of chromophore groups on the molecule and the interference caused by the high protein content of the samples hamper analysis. In this paper the development and qualification of a mixed-mode (MM) HPLC method with charged aerosol detection is reported. The method enables the analysis of samples with up to 85 g/L protein concentration. The range of the method was set to 250-500 μg/mL, where it was found to be accurate (89-111 % recovery) and precise (0.8-3.2 % relative standard deviation). The high sensitivity of the method indicates that even lower concentration range can be feasible. The novel method successfully demonstrates Pluronic F-68 clearance during the downstream process of the monoclonal antibody production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the presence of uncertainty, the optimum obtained based on a nominal identified model can neither provide any performance guarantee nor ensure that critical constraints are satisfied, which is crucial for e.g., bioprocess applications characterized by a high degree of complexity combined with costly experiments. Hence, uncertainty should be considered in the optimization and, furthermore, experiments designed to reduce the uncertainty most important for optimization. Herein, we propose a general framework that combines model-based robust optimization with optimal experiment design. The proposed framework can take advantage of prior knowledge in the form of a mechanistic model structure, and the importance of this is demonstrated by comparing it to more standard black-box models typically employed in learning. Through optimal experiment design, we repeatedly reduce the uncertainty most relevant for optimization so as to maximize the potential for improving the worst-case performance by balancing between exploration and exploitation. This makes the proposed method an efficient model-based robust optimization framework, especially in cases with limited experimental resources. The main part of the paper focuses on the case with modeling uncertainty that can be reduced with the availability of more experimental data. Towards the end of the paper, we consider extending the method to also include inherent uncertainty, such as input uncertainty and unmeasured disturbances. The effectiveness of the method is illustrated through a realistic simulation case study of medium optimization of Chinese hamster ovary cell cultivation in continuous monoclonal antibody production, where the metabolic network consists of 23 extracellular metabolites and 126 reactions. [ABSTRACT FROM AUTHOR]

Serological databases represent an important source of information to perceive COVID-19 impact on health professionals involved in combating the disease. This paper describes SerumCovid, a COVID-19 serological database focused on the diagnosis of health professionals, providing a preliminary analysis to contribute to the understanding of the antibody response to the SARS-CoV-2. The study population comprises 321 samples from 236 healthcare and frontline workers fighting COVID-19 in Vitória de Santo Antão, Brazil. Samples were collected from at least six days of symptoms to more than 100 days. The used immunoenzymatic assays were Euroimmun Anti-SARS-CoV-2 ELISA IgG and IgA. The most common gender in SerumCovid is female, while the most common age group is between 30 and 39 years old. However, no statistical differences were observed in either genders or age categories. The most reported symptoms were fatigue, headaches, and myalgia. Still, some subjects presented positive results for IgA after 130 days. Based on a temporal analysis, we have not identified general patterns as subjects presented high and low values of IgA and IgG with different evolution trends. Unexpectedly, for subjects with both serological tests, the outcome of IgA and IgG tests were the same (either positive or negative) for more than 80% of the samples. Therefore, SerumCovid helps better understand how COVID-19 affected healthcare and frontline workers, which increases knowledge about the infection and enables direct prevention actions. [ABSTRACT FROM AUTHOR]

Understanding the T-cell response to SARS-CoV-2 is key in patients who lack antibody production. We demonstrate the applicability of a functional assay to measure the T-cell response in a cohort of patients with immunodeficiency. T-cell responses to COVID are now linked to improved outcomes. This paper demonstrates a method to robustly test responses for routine diagnostic use in healthy controls and those unable to make a detectable antibody response due to underlying immune deficiency (primary or acquired). [ABSTRACT FROM AUTHOR]

Featured Application: The goal of this paper is to direct the discussion about individual risks and immunity breakthrough of infectious diseases, such as COVID-19, on quantitative effects concerning background and non-specific immunity, stimulation of antibody production and antibody decay, illustrated by a simple kinetic model. The personal risks of infection, as well as the conditions for achieving herd immunity, are strongly dependent on an individual's response to the infective agents on the one hand, and the individual's reactions to vaccination on the other hand. The main goal of this work is to illustrate the importance of quantitative individual effects for disease risk in a simple way. The applied model was able to illustrate the quantitative effects, in the cases of different individual reactions, after exposition to viruses or bacteria and vaccines. The model was based on simple kinetic equations for stimulation of antibody production using different concentrations of the infective agent, vaccine and antibodies. It gave a qualitative explanation for the individual differences in breakthrough risks and different requirements concerning a second, third or further vaccinations, reconsidering different efficiencies of the stimulation of an immune reaction. [ABSTRACT FROM AUTHOR]

Nickel (Ni) in ambient air may vary regionally with contributions from both natural processes and anthropogenic activities. Exposure to Ni compounds in ambient air above a certain level is associated with acute adverse effects, such as upper respiratory tract irritation, pneumonitis, and chronic adverse effects, such as respiratory cancer. Inhalation reference exposure standards are enacted in different jurisdictions to minimize exposures to ambient Ni above levels that can elicit adverse effects. This paper reports a guideline-/GLP-compliant study designed for setting inhalation exposure standards to protect from immunological effects associated with acute exposure to Ni. Female CD-1 mice were exposed via whole-body inhalation to aerosolized nickel chloride hexahydrate for 24-hr at nominal (vs. mean analyzed) concentrations of 20 (16), 50 (44) and 100 (81) µg Ni/m3. Host T-cell antibody immunological responses to intravenously-injected sheep red blood cells were then measured ex vivo in an Antibody-Forming Cell (AFC) assay. Exposure to the Ni substance significantly decreased spleen cell levels by 33%, but this was within biological variability for outbred mice. No concurrent decreases in spleen, thymus, or body weights were noted. No immunosuppression was observed with the Ni substance in the context of Total Spleen Activity [IgM AFC/spleen (× 103)] and Specific Activity [IgM AFC/spleen cells (× 106)]. Significant concentration-independent increases in Total Spleen Activity and Specific Activity seen with the nickel chloride hexahydrate were normal and within biological variability for outbred mice. In contrast, cyclophosphamide (positive control) significantly decreased spleen cell numbers, spleen and thymus weights, and abolished Specific Activity and Total Spleen Activity. Based on results here, an NOAEC of 81 µg Ni/m3 for immunosuppressive effects from inhaled nickel chloride hexahydrate was identified. It is hoped this value can be used to derive a reference standard for human exposure to ambient Ni. [ABSTRACT FROM AUTHOR]

This paper is concerned with the existence and nonexistence of traveling waves of a virus infection model with humoral immunity, cell‐to‐cell transmission, and general nonlinear incidence. Our results show that the existence of traveling wave solutions is determined not only by the basic reproduction number R0$$ {\mathcal{R}}_0 $$ of virus infection and the antibody response reproduction number R1$$ {\mathcal{R}}_1 $$ but also by the critical wave speed c∗$$ {c}^{\ast } $$. More precisely, we obtain the existence of traveling wave solution connecting infection‐free equilibrium and antibody‐free infection equilibrium for R0>1,R1<1$$ {\mathcal{R}}_0>1,{\mathcal{R}}_1<1 $$, and c>c∗$$ c>{c}^{\ast } $$ and connecting infection‐free equilibrium and antibody‐present infection equilibrium for R0>1,R1>1$$ {\mathcal{R}}_0>1,{\mathcal{R}}_1>1 $$, and c>c∗$$ c>{c}^{\ast } $$. The existence of traveling wave solution connecting infection‐free equilibrium and antibody‐present infection equilibrium is discussed. Some numerical simulations are carried out to illustrate our analytical results. [ABSTRACT FROM AUTHOR]

Some claims have been made that that Covid vaccination is effective against both infection and mortality, even though the WHO is seeking more evidence to determine how well vaccines stop infection and transmission. On the basis of UK daily data over the period 10 January 2021–6 January 2022, evidence is presented indicating that vaccination is not effective against infection but it is highly effective against mortality. This makes scientific sense because the function of vaccination is to stimulate the production of antibodies that fight off the virus, which does not imply the ability to stop infection. [ABSTRACT FROM AUTHOR]

Individuals with a history of coronavirus disease 2019 (COVID-19) exhibit memory immunity acquired during natural infection. However, a decline in immunity after infection renders these individuals vulnerable to re-infection, in addition to a higher risk of infection with new variants. This systematic review examined related studies to elucidate the antibody response in these infected individuals after messenger ribonucleic acid (mRNA) vaccination. Hence, the focus of this review was to ascertain differences in the concentration of binding and neutralising antibodies of previously infected individuals in comparison to those of infection-naïve individuals after administration of two doses of mRNA vaccination through available case-control and cohort studies. Positive reverse transcriptase-polymerase chain reaction (RT-PCR) test or detectable anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at the baseline in included studies showed categorisation of infected and uninfected individuals. This review utilised three online databases: PubMed, Scopus and Cochrane with the following keywords: (COVID-19 OR 'Coronavirus Disease 2019' OR SARS-CoV-2) AND Immun* AND (Pfizer OR BioNTech OR BNT162b2 OR Comirnaty OR Moderna OR mRNA-1273) from January 2019 to July 2021. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) 2020 guidelines and assessment based on the Crowe Critical Appraisal Tool (CCAT), we included 13 related qualified papers of observational studies discerning the binding and neutralising antibody concentrations of infected and uninfected individuals after administration of mRNA vaccines, such as the BNT162b2 and mRNA-1273 vaccine. The mRNA vaccines induced robust binding and neutralising antibody responses in both groups. However, infected individuals showed induction of higher antibody responses in a shorter time compared to uninfected individuals. Hence, a single dose of mRNA vaccination for infected individuals may be sufficient to reach the same level of antibody concentration as that observed in uninfected individuals after receiving two doses of vaccination. [ABSTRACT FROM AUTHOR]

Sablefish (Anoplopoma fimbria) are an emerging aquaculture species native to the continental shelf of the northern Pacific Ocean. There is limited information on both innate and adaptive immunity for this species and new tools are needed to determine antibody response following vaccination or disease outbreaks. In this paper, a monoclonal antibody, UI-25A, specific to sablefish IgM was produced in mice. Western blotting confirmed UI-25A recognizes the heavy chain of IgM and does not cross react to proteins or carbohydrates in serum of four other teleost species. An ELISA was developed to measure Aeromonas salmonicida specific IgM in the plasma of sablefish from a previous experiment where fish were immunized with a proprietary A. salmonicida vaccine. UI-25A was used in Western blot analyses to identify immunogenic regions of A. salmonicida recognized by this specific IgM from vaccinated sablefish. Immunofluorescent staining also demonstrated the ability of UI-25A to recognize membrane-bound IgM and identify IgM + cells in the head kidney. These results demonstrate the usefulness of UI-25A as a tool to improve the understanding of antibody-mediated immunity in sablefish as well as to provide valuable information for vaccine development and expansion of aquaculture efforts for this fish species. • A mAb, UI-25A, specific to the heavy chain of sablefish IgM is produced. • The mAb detects differences in A. salmonicida antibody titers after vaccination. • The mAb detects immunogenic regions of A. salmonicida via western blotting. • The UI-25A mAb also detects IgM + cells using immunofluorescent microscopy. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) have emerged as the dominant class of therapeutic moieties due to their superior therapeutic potential and safety profile. Downstream processing plays a pivotal role in ensuring the purity, yield, and quality of these therapeutic products. The biopharmaceutical industry generates a significant amount of data, making it an attractive target for creating machine learning (ML) and deep learning (DL) applications. This paper reports a DL-based 2D-convolutional neural network (2D-CNN) to predict: (i) Protein A mAb elute concentration, (ii) Cation exchange (CEX) mAb elute concentration, (iii) % Acidic variant, (iv) Aggregate (%), and (v) % Basic variant from process data that is routinely collected during biopharma manufacturing, including Protein A elution UV, CEX elution UV, CEX elution conductivity, and post viral inactivation pH profiles. Further, interpretation of predicted outputs using the SHAPLEY technique and optimization through multi-objective Bayesian optimization methods have been attempted so as to match the biosimilar to the reference molecule with respect to the critical quality attributes. It is observed that the proposed model outperforms other published approaches in prediction. The optimum results were experimentally validated by performing three consecutive runs, and a mean percentage deviation of less than 3 % was reported. The proposed approach demonstrates the feasibility of real-time prediction and optimization in biopharmaceutical product manufacturing using CNN-aided modeling and multi-objective weighted sum optimization. [Display omitted] • A data-driven 2D CNN model is implemented for prediction of output variables. • SHAPLEY technique is employed for model interpretation. • Bayesian optimization is utilized for attaining optimum target variables. • Experimental verification of optimum output is performed with three runs. [ABSTRACT FROM AUTHOR]