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This investigation elucidated the differences in humoral and H1N1 HA-specific memory B-cells response in participants exhibiting distinct immune response patterns prior to and after vaccination with Fluzone, the quadrivalent split-inactivated seasonal influenza virus vaccine. Participants were categorized into persistent non-responders and persistent responders based on their hemagglutination-inhibition (HAI) antibody titers to the H1N1 component from each vaccine administered between the 2019-2020 to 2023-2024 seasons. Persistent responders had higher fold change in H1N1 HA-specific CD21 expressing B-cells, plasmablasts, and plasma cells. A significant increase in H1N1 HA-specific transitional B-cells in persistent non-responders was observed. The frequency and fold change of H1N1-specific IgM-expressing memory B-cells was higher in persistent non-responders. Dimensionality reduction analysis also demonstrated higher IgM expression for persistent non-responders than persistent responders. Furthermore, persistent non-responders had a significant fold change increase in IgA tissue-like memory, IgG exhausted tissue-like memory, and double negative (DN) activated memory cells. In contrast, persistent responders had increased frequency of IgG-activated memory B-cells, IgG resting B-cells and DN resting B-cells. Correlation analysis revealed a positive correlation between HAI titers and DN memory B-cells and a negative correlation between HAI titers and IgG-expressing memory B-cells in persistent non-responders. Conversely, persistent responders had a positive correlation between HAI titers and IgA resting memory B-cells and a negative correlation between IgG memory B-cells and DN memory B-cells. Overall, this study provided valuable insights into the differential immune memory B-cell responses following influenza virus vaccination and paves the way for future research to further unravel the complexities of vaccine-induced memory B-cells and ultimately improve vaccination strategies against influenza virus infection. [ABSTRACT FROM AUTHOR]

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre‐Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) specific antibodies including total antibodies, anti‐receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS‐CoV‐2 wild type (WT) and BA.4/5 variant. T cell responses against SARS‐CoV‐2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron‐infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long‐lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p <.05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p =.0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non‐reinfected patients (all p <.05), and those patients of unvaccinated at late stage receiving anti‐cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection. [ABSTRACT FROM AUTHOR]

Dirofilaria repens is a zoonotic parasitic filarial nematode that infects carnivores and occasionally humans. Knowledge of the host–parasite molecular interactions enabling the parasite’s avoidance of the host immune response in subcutaneous dirofilariasis remains limited. Parasitic orthologues of host macrophage migration inhibitory factor (MIF) are molecules potentially involved in this process.

Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1–28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor discussing the need to update the current COVID-19 vaccine due to the emergence of new variants of the SARS-CoV-2 virus. The authors conducted a study to evaluate the neutralizing antibody response against two specific variants, KP.2 and KP.3, in individuals who received a specific booster vaccine. The results showed a significant decrease in neutralizing antibody titers against these variants, indicating the importance of adapting future vaccines to address these emerging variants. The authors emphasize the need for ongoing research and adaptation of the vaccine to stay ahead of evolving viral strains, while also considering the effectiveness of the T cell response against highly mutated variants. [Extracted from the article]

Background: Vaccination is one of the most effective medical interventions to prevent infectious diseases. The introduction of vaccines against coronavirus acute respiratory syndrome 2 (SARS-CoV-2) was aimed at preventing severe illness and death due to coronavirus disease 2019 (COVID-19). Solid organ transplant recipients (SOTRs) are at high risk of infection with SARS-CoV-2 and serious effects associated with COVID-19, mainly due to the use of immunosuppressive therapies, which further cause suboptimal response to COVID-19 vaccination. Aim of the study: We aimed to compare post-vaccination response to BNT162b2 in kidney–pancreas transplant recipient, specifically in immunocompetent individuals, over two years of simultaneous monitoring. Methods: To determine the humoral response, the levels of the IgG and IgA anti-S1 antibodies were measured. To assess the cellular response to SARS-CoV-2, the released IFN-γ-S1 was determinate. Results and Conclusion: After primary vaccination, compared to immunocompetent subjects, SOTR showed lower seroconversion for both antibody classes. Only the additional dose produced antibodies at the level reached by the control group after the baseline vaccination. During the monitored period, SOTR did not achieve a positive cellular response in contrast to immunocompetent individuals, so in order to obtain longer protection, including immune memory, the adoption of booster doses of the vaccine should be considered. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Although our understanding of the pandemic has improved significantly since the beginning, the natural history of COVID-19 and its impacts on under-represented populations, such as Indigenous people from America, remain largely unknown. We performed a retrospective serological survey with two Brazilian Indigenous populations (n=624), Tupiniquim and Guarani-Mbya'. Samples were collected between September 2020 and July 2021: a period comprising the dissemination of SARS-CoV-2 variants and the beginning of COVID-19 vaccination in Brazil. Seroconversions against S and N antigens were assessed using three different commercially available ELISA kits. Samples were also used to assess the prevalence of tuberculosis (TB) in the same population (n=529). Seroconversion against SARS-CoV-2 antigens was considered positive if at least one of the three ELISA kits detected levels of specific antibodies above the threshold specified by the manufacturer. In this sense, we report 56.0% (n=349/623) of seroconverted individuals. Relative seroconversion peaked after introduction of the Coronavac vaccine in February 2021. Vaccination increased the production of anti-S IgG from 3.9% to 48.6%. Our results also indicated that 11.0% (n=46/417) of all individuals were positive for TB. Seroconversion to SARSCoV-2 was similar between individuals with positive tuberculosis test results to those with negative test results. Most vaccinated individuals seroconverted to SARS-CoV-2, indicating that Coronavac may be as protective in individuals from these indigenous groups as observed in the general Brazilian population. COVIDFrontiers 19 severity was minimal regardless of incomplete vaccine coverage, suggesting that vaccination may not be the only factor protecting individuals from severe COVID-19. Tuberculosis is highly prevalent and not associated with increased seroconversion to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population. [ABSTRACT FROM AUTHOR]

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) causes reproductive failure and respiratory symptoms, leading to huge economic losses for the pig farming industry. Although several vaccines against PRRSV are available in the market; they show an overall low efficacy, and several countries have the need for vaccines covering the local, circulating variants. This project aims at developing a new chimeric antigen targeting specific epitopes from PRRSV and evaluating two test adjuvants to formulate a vaccine candidate. The test antigen was called LTB–PRRSV, which was produced recombinantly in Escherichia coli and consisted of the heat labile enterotoxin B subunit from E. coli (LTB) and four epitopes from PRRSV. LTB–PRRSV was rescued as inclusion bodies and methods for its solubilization, IMAC-based purification, and refolding were standardized, leading to mean yields of 18 mg of pure protein per liter culture. Layered double hydroxides (LDH) have been used as vaccine adjuvants given their biocompatibility, low cost, and positive surface charge that allows an efficient adsorption of negatively charged biomolecules. Therefore, LDH were selected as delivery vehicles of LTB–PRRSV. Pure LTB–PRRSV was adsorbed onto LDH by incubation at different LDH:LTB–PRRSV mass ratios (1:0.25, 1:0.5, 1:1, and 1:2) and at pH 9.5. The best adsorption occurred with a 1:2 mass ratio, and in a sucrose-tween solution. The conjugates obtained had a polydispersity index of 0.26, a hydrodynamic diameter of 192 nm, and a final antigen concentration of 64.2 μg/mL. An immunogenicity assessment was performed by injecting mice with LDH:LTB–PRRSV, Alum/LTB–PRRSV, or LTB–PRRSV in a scheme comprising three immunizations at two-week intervals and two dose levels (1 and 5 μg). LTB–PRRSV was capable of inducing strong humoral responses, which lasted for a longer period when LDH was used as the delivery vehicle/adjuvant. The potential of LDH to serve as an attractive carrier for veterinary vaccines is discussed. [ABSTRACT FROM AUTHOR]

HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity. [ABSTRACT FROM AUTHOR]

We recently showed that an adapted SARS-CoV-2 vaccine with wildtype and BA.4/BA.5 Omicron subtype epitopes induced a broad short-term immune response in hemodialysis patients. Antibodies with protective capacity were boosted significantly after a follow-up period of 3 weeks following a fifth vaccine dose. However, data on the longevity of the humoral response after bivalent vaccination are lacking but urgently needed to make recommendations for further booster vaccinations in this patient group. This study is an extension of our previously published data including 40 patients on hemodialysis with a follow-up period of 12 months after an adapted booster vaccine dose. We performed a detailed characterization of humoral immune responses and assessed breakthrough infections. In addition, the severity of breakthrough infections was assessed using an established grading system. Anti-S1 IgG and surrogate neutralizing antibodies significantly decreased during the period of 12 months (p < 0.01 and p < 0.001, respectively). Live-virus neutralizing antibodies against the wildtype and the BA.5 subtype also significantly decreased over time (p < 0.01 and p < 0.01, respectively). However, even 12 months after administration of the adapted vaccine dose, all 40/40 (100%) of hemodialysis patients showed detectable SARS-CoV-2 wildtype neutralization activity, with 35/40 (88%) also exhibiting detectable BA.5 subtype neutralization activity. During follow-up, 13/40 (33%) patients contracted a SARS-CoV-2 breakthrough infection, among which 12 cases were categorized as asymptomatic or mild, while only 1 case was classified as moderate disease activity. Thus, bivalent booster vaccination seems to induce a sustained immune response in hemodialysis patients over a period of 12 months with breakthrough infections occurring frequently but predominantly manifesting as asymptomatic or mild. [ABSTRACT FROM AUTHOR]

BackgroundBullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) are rare autoimmune blistering disorders characterized by autoantibodies (autoAbs) targeting dermo-epidermal junction components such as BP180 and BP230. The differential diagnosis, based on both the time of appearance and the extension of cutaneous and/or mucosal lesions, is crucial to distinguish these diseases for improving therapy outcomes and delineating the correct prognosis; however, in some cases, it can be challenging. In addition, negative results obtained by commercially available enzyme-linked immunosorbent assays (ELISAs) with BP and MMP sera, especially from patients with ocular involvement, often delay diagnosis and treatment, leading to a greater risk of poor outcomes.ObjectivesOur aim was to find potentially different reactivity profiles in BP and MMP and improve available approaches for diagnosis with focus on ocular MMP.MethodsTwo cohorts of 90 BP and 90 MMP, recruited from different Italian clinical centers, were characterized also employing a novel ELISA based on the BP180 extracellular domain (ECD-BP180).ResultsImmunoglobulin G (IgG) reactivity to BP180 and BP230 in MMP sera was significantly reduced in comparison with BP, mostly affecting BP230 and E-1080 (53% and 36% in BP vs. 11% and 3% in MMP, respectively, p < 0.0001). The combined sensitivity of BP180-NC16A and ECD-BP180 ELISAs was greater compared to BP180-NC16A and BP230 ELISAs both in BP (97% and 92%, respectively) and in MMP (42% and 31%, respectively). The present study shows that MMP patients with ocular involvement rarely reacted to BP180 by IgG in contrast with patients with oral and/or cutaneous involvement (p = 0.0245 and p = 0.0377, respectively), suggesting that an oral and/or cutaneous MMP positive to BP180 hardly evolves to ocular MMP. Of note, one-third of ocular MMP showed immunoglobulin A (IgA) reactivity to ECD-BP180 by immunoblotting.ConclusionsThe present study provides several hints to perform a correct and timely diagnosis in BP and MMP, which is crucial for improving therapy outcomes and delineating the correct prognosis.

This investigation elucidated the differences in humoral and H1N1 HA-specific memory B-cells response in participants exhibiting distinct immune response patterns prior to and after vaccination with Fluzone, the quadrivalent split-inactivated seasonal influenza virus vaccine. Participants were categorized into persistent non-responders and persistent responders based on their hemagglutination-inhibition (HAI) antibody titers to the H1N1 component from each vaccine administered between the 2019-2020 to 2023-2024 seasons. Persistent responders had higher fold change in H1N1 HA-specific CD21 expressing B-cells, plasmablasts, and plasma cells. A significant increase in H1N1 HA-specific transitional B-cells in persistent non-responders was observed. The frequency and fold change of H1N1-specific IgM-expressing memory B-cells was higher in persistent non-responders. Dimensionality reduction analysis also demonstrated higher IgM expression for persistent non-responders than persistent responders. Furthermore, persistent non-responders had a significant fold change increase in IgA tissue-like memory, IgG exhausted tissue-like memory, and double negative (DN) activated memory cells. In contrast, persistent responders had increased frequency of IgG-activated memory B-cells, IgG resting B-cells and DN resting B-cells. Correlation analysis revealed a positive correlation between HAI titers and DN memory B-cells and a negative correlation between HAI titers and IgG-expressing memory B-cells in persistent non-responders. Conversely, persistent responders had a positive correlation between HAI titers and IgA resting memory B-cells and a negative correlation between IgG memory B-cells and DN memory B-cells. Overall, this study provided valuable insights into the differential immune memory B-cell responses following influenza virus vaccination and paves the way for future research to further unravel the complexities of vaccine-induced memory B-cells and ultimately improve vaccination strategies against influenza virus infection.

Abstract Assessing the prevalence of SARS-CoV-2 IgG positivity through population-based serological surveys is crucial for monitoring COVID-19 vaccination efforts. In this study, we evaluated SARS-CoV-2 IgG positivity within a provincial cohort to understand the magnitude of the humoral response against the SARS-CoV-2 vaccine and to inform evidence-based public health decisions. A community-based cross-sectional seroprevalence study was conducted, involving 10,669 participants who received various vaccines (two doses for BBIBP-CorV/Sinopharm, Covishield vaccine, and Pfizer/BioNTech, and one dose for Johnson & Johnson's Janssen COVID-19 vaccine). The study spanned 16 provinces in the Casablanca-Settat region from February to June 2022, during which comprehensive demographic and comorbidity data were collected. We screened samples for the presence of IgG antibodies using the SARS-CoV-2 IgG II Quant assay, which quantifies antibodies against the receptor-binding domain (RBD) of the spike (S) protein, measured on the Abbott Architect i2000SR. The overall crude seroprevalence was 96% (95% CI: 95.6–96.3%), and after adjustment for assay performance, it was estimated as 96.2% (95% CI: 95.7–96.6). The adjusted overall seroprevalences according to vaccine brands showed no significant difference (96% for BBIBP-CorV/Sinopharm, 97% for ChAdOx1 nCoV-19/Oxford/AstraZeneca, 98.5% for BNT162b2/Pfizer-BioNTech, and 98% for Janssen) (p = 0.099). Participants of older age, female sex, those with a history of previous COVID-19 infection, and those with certain chronic diseases were more likely to be seropositive among ChAdOx1 nCoV-19/Oxford/AstraZeneca and BBIBP-CorV/Sinopharm vaccinee groups. Median RBD antibody concentrations were 2355 AU/mL, 3714 AU/mL, 5838 AU/mL, and 2495 AU/mL, respectively, after two doses of BBIBP-CorV/Sinopharm, ChAdOx1 nCoV-19/Oxford/AstraZeneca, BNT162b2/Pfizer-BioNTech, and after one dose of Janssen (p 0.05). In conclusion, our serosurvey findings indicate that all four investigated vaccines provide a robust humoral immune response in the majority of participants (more than 96% of participants had antibodies against SARS-CoV-2). The BNT162b2 vaccine was found to be effective in eliciting a strong humoral response compared to the other three vaccines. However, challenges still remain in examining the dynamics and durability of immunoprotection in the Moroccan context.

The Zika virus (ZIKV) is considered a public health problem worldwide due to its association with the development of microcephaly and the Guillain-Barré syndrome. Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is a relevant goal. In this study, a multi-epitope protein called rpZDIII was designed based on a series of ZIKV antigenic sequences, a bacterial carrier, and linkers. The analysis of the predicted 3D structure of the rpZDIII chimeric antigen was performed on the AlphaFold 2 server, and it was produced in E. coli and purified from inclusion bodies, followed by solubilization and refolding processes. The yield achieved for rpZDIII was 11 mg/L in terms of pure soluble recombinant protein per liter of fermentation. rpZDIII was deemed immunogenic since it induced serum IgG and IgM responses in mice upon subcutaneous immunization in a three-dose scheme. Moreover, sera from mice immunized with rpZDIII showed neutralizing activity against ZIKV. Therefore, this study reveals rpZDIII as a promising immunogen for the development of a rationally designed multi-epitope vaccine against ZIKV, and completion of its preclinical evaluation is guaranteed. [ABSTRACT FROM AUTHOR]

Takayasu's arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The precise etiology of TAK remains elusive, with current understanding suggesting an autoimmune origin primarily driven by T cells. Notably, a growing body of evidence bears testimony to the widespread effects of B cells on disease pathogenesis and progression. Distinct alterations in peripheral B cell subsets have been described in individuals with TAK. Advancements in technology have facilitated the identification of novel autoantibodies in TAK. Moreover, emerging data suggest that dysregulated signaling cascades downstream of B cell receptor families, including interactions with innate pattern recognition receptors such as toll-like receptors, as well as co-stimulatory molecules like CD40, CD80 and CD86, may result in the selection and proliferation of autoreactive B cell clones in TAK. Additionally, ectopic lymphoid neogenesis within the aortic wall of TAK patients exhibits functional characteristics. In recent decades, therapeutic interventions targeting B cells, notably utilizing the anti-CD20 monoclonal antibody rituximab, have demonstrated efficacy in TAK. Despite the importance of the humoral immune response, a systematic understanding of how autoreactive B cells contribute to the pathogenic process is still lacking. This review provides a comprehensive overview of the biological significance of B cell-mediated autoimmunity in TAK pathogenesis, as well as insights into therapeutic strategies targeting the humoral response. Furthermore, it examines the roles of T-helper and T follicular helper cells in humoral immunity and their potential contributions to disease mechanisms. We believe that further identification of the pathogenic role of autoimmune B cells and the underlying regulation system will lead to deeper personalized management of TAK patients. We believe that further elucidation of the pathogenic role of autoimmune B cells and the underlying regulatory mechanisms holds promise for the development of personalized approaches to managing TAK patients. [ABSTRACT FROM AUTHOR]

Introduction: Antibody production and the generation of memory B cells are regulated by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in germinal centers. However, the precise role of Tfr cells in controlling antibody production is still unclear. We have previously shown that both Tfh and Tfr cells express the IL-1R1 agonist receptor, whereas only Tfr cells express the IL-1R2 decoy and IL-1Ra antagonist receptors. We aimed to investigate the role of IL-1 receptors in the regulation of B cell responses by Tfh and Tfr. Methods: We generated mice with IL-1 receptors inactivated in Tfh or Tfr and measured antibody production and cell activation after immunisation. Results: While IL-1β levels are increased in the draining lymph node after immunisation, antigen-specific antibody levels and cell phenotypes indicated that IL-1β can activate both Tfh and Tfr cells through IL-1R1 stimulation. Surprisingly, expression of IL-1R2 and IL-1Ra on Tfr cells does not block IL-1 activation of Tfh cells, but rather prevents IL-1/IL-1R1-mediated early activation of Tfr cells. IL-1Rs also regulate the antibody response to autoantigens and its associated pathophysiology in an experimental lupus model. Discussion: Collectively, our results show that IL-1 inhibitory receptors expressed by Tfr cells prevent their own activation and suppressive function, thus licensing IL-1-mediated activation of Tfh cells after immunisation. Further mechanistic studies should unravel these complex interactions between IL-1b and follicular helper and regulatory T cells and provide new avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8+ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8+ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8+ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8+ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Novel mechanisms of COVID-19 vaccines raised concern about their potential immunogenicity in patients with rheumatoid arthritis (RA) undergoing immunomodulatory treatments. We designed a retrospective single-center study to investigate their effectiveness and safety in this population, analyzing data from the first vaccination program (December 2020–October 2021). Inclusion criteria were availability of post-vaccination serology and a minimum subsequent follow-up of 6 months. Binding antibody units (BAU/mL) ≥ 7.1 defined an adequate serological response. Post-vaccine COVID-19 incidence and its timing since vaccination, adverse events (AEs), and RA flares were recorded. Adjusted logistic and linear multivariate regression analyses were carried out to identify factors associated with vaccine response. We included 118 patients (87.2% women, age 65.4 ± 11.6 years, evolution 12.0 ± 9.6 years), of whom 95.8% had a complete vaccination schedule. Adequate humoral immunogenicity was achieved in 88.1% of patients and was associated with previous COVID-19 and mRNA vaccines, whereas smoking, aCCP, age, and DMARDs exerted a negative impact. Post-vaccine COVID-19 occurred in 18.6% of patients, a median of 6.5 months after vaccination. Vaccine AE (19.5%) and RA flares (1.7%) were mostly mild and inversely associated with age. Our results suggest that COVID-19 vaccines induce adequate humoral immunogenicity, with an acceptable safety profile in RA patients. [ABSTRACT FROM AUTHOR]

Cancer patients (CPs), being immunosuppressed due to the treatment received or to the disease itself, are more susceptible to infections and their potential complications, showing therefore an increased risk of developing severe COVID-19 compared to the general population. We evaluated the immune responses to anti-SARS-CoV-2 vaccination in patients with solid tumors one year after the administration of the third dose and the effect of cancer treatment on vaccine immunogenicity was assessed. Healthy donors (HDs) were enrolled. Binding and neutralizing antibody (Ab) titers were evaluated using chemiluminescence immunoassay (CLIA) and Plaque Reduction Neutralization Test (PRNT) respectively. T-cell response was analyzed using multiparametric flow cytometry. CPs who were administered three vaccine doses showed lower Ab titers than CPs with four doses and HDs. Overall, a lower cell-mediated response was found in CPs, with a predominance of monofunctional T-cells producing TNFα. Lower Ab titers and a weaker T-cell response were observed in CPs without prior SARS-CoV-2 infection when compared to those with a previous infection. While no differences in the humoral response were found comparing immunotherapy and non-immunotherapy patients, a stronger T-cell response in CPs treated with immunotherapy was observed. Our results emphasize the need of booster doses in cancer patients to achieve a level of protection similar to that observed in healthy donors and underlines the importance of considering the treatment received to reach a proper immune response. [ABSTRACT FROM AUTHOR]

Assessing the prevalence of SARS-CoV-2 IgG positivity through population-based serological surveys is crucial for monitoring COVID-19 vaccination efforts. In this study, we evaluated SARS-CoV-2 IgG positivity within a provincial cohort to understand the magnitude of the humoral response against the SARS-CoV-2 vaccine and to inform evidence-based public health decisions. A community-based cross-sectional seroprevalence study was conducted, involving 10,669 participants who received various vaccines (two doses for BBIBP-CorV/Sinopharm, Covishield vaccine, and Pfizer/BioNTech, and one dose for Johnson & Johnson's Janssen COVID-19 vaccine). The study spanned 16 provinces in the Casablanca-Settat region from February to June 2022, during which comprehensive demographic and comorbidity data were collected. We screened samples for the presence of IgG antibodies using the SARS-CoV-2 IgG II Quant assay, which quantifies antibodies against the receptor-binding domain (RBD) of the spike (S) protein, measured on the Abbott Architect i2000SR. The overall crude seroprevalence was 96% (95% CI: 95.6–96.3%), and after adjustment for assay performance, it was estimated as 96.2% (95% CI: 95.7–96.6). The adjusted overall seroprevalences according to vaccine brands showed no significant difference (96% for BBIBP-CorV/Sinopharm, 97% for ChAdOx1 nCoV-19/Oxford/AstraZeneca, 98.5% for BNT162b2/Pfizer-BioNTech, and 98% for Janssen) (p = 0.099). Participants of older age, female sex, those with a history of previous COVID-19 infection, and those with certain chronic diseases were more likely to be seropositive among ChAdOx1 nCoV-19/Oxford/AstraZeneca and BBIBP-CorV/Sinopharm vaccinee groups. Median RBD antibody concentrations were 2355 AU/mL, 3714 AU/mL, 5838 AU/mL, and 2495 AU/mL, respectively, after two doses of BBIBP-CorV/Sinopharm, ChAdOx1 nCoV-19/Oxford/AstraZeneca, BNT162b2/Pfizer-BioNTech, and after one dose of Janssen (p < 0.0001). Furthermore, we observed that participants vaccinated with ChAdOx1 nCoV-19/Oxford/AstraZeneca and BBIBP-CorV/Sinopharm with comorbid chronic diseases exhibited a more pronounced response to vaccination compared to those without comorbidities. In contrast, no significant differences were observed among Pfizer-vaccinated participants (p > 0.05). In conclusion, our serosurvey findings indicate that all four investigated vaccines provide a robust humoral immune response in the majority of participants (more than 96% of participants had antibodies against SARS-CoV-2). The BNT162b2 vaccine was found to be effective in eliciting a strong humoral response compared to the other three vaccines. However, challenges still remain in examining the dynamics and durability of immunoprotection in the Moroccan context. [ABSTRACT FROM AUTHOR]

Background Vaccination plays a critical role in mitigating the burden associated with yellow fever (YF). However, there is a lack of comprehensive evidence on the humoral response to primary vaccination in the paediatric population, with several questions debated, including the response when the vaccine is administered at early ages, the effect of co-administration with other vaccines, the duration of immunity and the use of fractional doses, among others. This study summarizes the existing evidence regarding the humoral response to primary YF vaccination in infants and children. Methods Studies on the humoral response to primary YF vaccination in children aged 12 years or younger were reviewed. The humoral vaccine response rate (VRR), i.e. the proportion of children who tested positive for vaccine-induced YF-specific neutralizing antibodies, was pooled through random-effects meta-analysis and categorized based on the time elapsed since vaccination. Subgroup, meta-regression and sensitivity analyses were performed. Results A total of 33 articles met the inclusion criteria, with all but one conducted in countries where YF is endemic. A total of 14 028 infants and children entered this systematic review. Within three months following vaccination, the pooled VRR was 91.9% (95% CI 89.8–93.9). A lower VRR was observed with the 17DD vaccine at the meta-regression analysis. No significant differences in immunogenicity outcomes were observed based on age, administration route, co-administration with other vaccines, or fractional dosing. Results also indicate a decline in VRR over time. Conclusions Primary YF vaccination effectively provides humoral immunity in paediatric population. However, humoral response declines over time, and this decline is observable after the first 18 months following vaccination. A differential response according to the vaccine substrain was also observed. This research has valuable implications for stimulating further research on the primary YF vaccination in infants and children, as well as for informing future policies. [ABSTRACT FROM AUTHOR]

While micronutrients are crucial for immune function, their impact on humoral responses to inactivated COVID‐19 vaccination remains unclear. We investigated the associations between seven key micronutrients and antibody responses in 44 healthy adults with two doses of an inactivated COVID‐19 vaccine. Blood samples were collected pre‐vaccination and 28 days post‐booster. We measured circulating minerals (iron, zinc, copper, and selenium) and vitamins (A, D, and E) concentrations alongside antibody responses and assessed their associations using linear regression analyses. Our analysis revealed inverse associations between blood iron and zinc concentrations and anti‐SARS‐CoV‐2 IgM antibody binding affinity (AUC for iron: β = −258.21, p < 0.0001; zinc: β = −17.25, p = 0.0004). Notably, antibody quality presented complex relationships. Blood selenium was positively associated (β = 18.61, p = 0.0030), while copper/selenium ratio was inversely associated (β = −1.36, p = 0.0055) with the neutralizing ability against SARS‐CoV‐2 virus at a 1:10 plasma dilution. There was no significant association between circulating micronutrient concentrations and anti‐SARS‐CoV‐2 IgG binding affinity. These findings suggest that circulating iron, zinc, and selenium concentrations and copper/selenium ratio, may serve as potential biomarkers for both quantity (binding affinity) and quality (neutralization) of humoral responses after inactivated COVID‐19 vaccination. Furthermore, they hint at the potential of pre‐vaccination dietary interventions, such as selenium supplementation, to improve vaccine efficacy. However, larger, diverse studies are needed to validate these findings. This research advances the understanding of the impact of micronutrients on vaccine response, offering the potential for personalized vaccination strategies. [ABSTRACT FROM AUTHOR]

Several disturbances in T-cell mediated immunity have been described during aging, but immunosenescence of the B-cell compartment is less well elucidated. The peripheral blood B-cell compartment (CD19+) can be split into six main subpopulations according to the cell surface markers IgD, CD27, CD24, and CD38: Transitional, naïve, unswitched, switched, double negative and plasmablasts. We thus aimed to verify whether shifts in these subsets occur during healthy and pathological aging. We recruited three groups of aged people (> 60 years old), healthy, COPD patients, and smokers without altered pulmonary function test, and a fourth group of individuals 18–40 years old (youngs). Total B-cells percentage and absolute number were similar among the healthy aged, COPD patients, and youngs, but the smokers showed significantly higher absolute numbers. While all six B-cell subset percentages were comparable among the healthy aged, COPD patients, and youngs, smokers showed significantly higher percentages of switched B-cells and reduced naïve B-cells than the other three groups, resulting in an inverted naive:switched ratio. Analysis of the cell subset absolute numbers showed a similar trend. Overall, our results suggest that aging drives milder alterations in the distribution of peripheral blood B-cell subpopulations than in the T-cell compartment. We suggest that it is the T-cell immunosenescence that most contributes to the poor humoral immune responses in the elderly, vaccine responses included. Surprisingly it was the smokers who showed significant alterations when compared with the youngs, healthy aged, and aged COPD patients, probably as a result of the chronic immune stimulation described in active smoking subjects. [ABSTRACT FROM AUTHOR]

Introduction: Some studies suggest that the monovalent mRNA-1273 vaccine is more effective than BNT162b2 in producing higher levels of antibodies. However, limited data are available, and the methods used are not directly comparable. Material and methods: Blood samples were obtained before the booster (third dose) and after 14, 90, and 180 days in two similar cohorts who received the original BNT162b2 or mRNA-1273 vaccine designed to target wild type SARS-CoV-2. The aim of our study is to compare their effectiveness by assessing the levels of binding and neutralizing antibodies specifically against each of the BA.1 variant, BA.5 variant, and the XBB.1.5 subvariant. Results: Once the peak was reached after two weeks, a drastic decline in binding and neutralizing antibodies was observed up to 6 months after the homologous booster administration. The humoral response was however more sustained with the mRNA-1273 booster, with half-lives of 167, 55, and 48 days for binding, BA.1, and BA.5 neutralizing antibodies compared to 144, 30, and 29 days for the BNT162b2 booster, respectively. Compared to the BA.1 variant, the neutralizing capacity was significantly decreased at 6 months with the BA.5 variant (fold-decrease: 1.67 to 3.20) and the XBB.1.5. subvariant (fold-decrease: 2.86 to 5.48). Conclusion: Although the decrease in the humoral response was observed with both mRNA vaccines over time, a more sustained response was observed with the mRNA-1273 vaccine. Moreover, the emergence of Omicron-based variants causes a reduced neutralizing capacity, notably with the XBB.1.5. subvariant. The administration of subsequent boosters would therefore be needed to restore a sufficiently high neutralizing response.

ABSTRACT Since Porcine Circovirus 3 (PCV3) was first identified in 2016, our understanding of the humoral response is still relatively scarce. Current knowledge of the PCV3 humoral response is primarily based on field studies identifying the seroprevalence of PCV3 Cap-induced antibodies. Studies on the humoral response following experimental PCV3 infection have conflicting results where one study reports the development of the Cap IgG response 7 days postinfection with no concurrent Cap IgM response, while a second study shows a Cap IgM response at the same time point with no detection of Cap IgG. The dynamics of the PCV3 Cap and Rep IgG following maternal antibody transfer and experimental infection have not been well characterized. Additionally, the cross-reactivity of convalescent serum from PCV2 and PCV3 experimentally infected animals to serologic methods of the alternate PCV has limited evaluation. Here, we show that maternally derived antibodies were detectable in piglet serum 7–9 weeks postfarrowing for the Cap IgG and 5-weeks-post farrowing for the Rep IgG using Cap- and Rep-specific enzyme linked immunosorbent assays (ELISA) and immunofluorescent assays (IFA) methods. Following experimental inoculation, Cap IgG was detected at 2-weeks-post inoculation and Rep IgG detection was delayed until 4-weeks-post inoculation. Furthermore, convalescent serum from either PCV2 or PCV3 methods displayed no cross-reactivity by serological methods against the other PCV. The information gained in this study highlights the development of both the Cap- and Rep-specific antibodies following experimental infection and through the transfer of maternal antibodies. The increased understanding of the dynamics of maternal antibody transfer and development of the humoral response following infection gained in the present study may aid in the establishment of husbandry practices and potential application of prophylactics to control PCV3 clinical disease.IMPORTANCEResearch on Porcine Circovirus 3 (PCV3) immunology is vital for understanding and controlling this virus. Previous studies primarily relied on field observations, but they have shown conflicting results about the immunological response against PCV3. This study helps fill those gaps by looking at how antibodies develop in pigs, especially those maternal-derived, and their impact in neonatal pigs preventing PCV3-associated disease in piglets. In addition, we look at the dynamics of antibodies in experimental infections mimicking infection in pigs in the grower-phase condition. Understanding this process can help to develop better strategies to prevent PCV3 infection. Also, this research found that PCV2 and PCV3 do not cross-react, which is crucial for serological test development and results interpretation. Overall, this work is essential for improving swine health and farming practices in the face of PCV3 infections.

The COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Although our understanding of the pandemic has improved significantly since the beginning, the natural history of COVID-19 and its impacts on under-represented populations, such as Indigenous people from America, remain largely unknown. We performed a retrospective serological survey with two Brazilian Indigenous populations (n=624), Tupiniquim and Guarani-Mbyá. Samples were collected between September 2020 and July 2021: a period comprising the dissemination of SARS-CoV-2 variants and the beginning of COVID-19 vaccination in Brazil. Seroconversions against S and N antigens were assessed using three different commercially available ELISA kits. Samples were also used to assess the prevalence of tuberculosis (TB) in the same population (n=529). Seroconversion against SARS-CoV-2 antigens was considered positive if at least one of the three ELISA kits detected levels of specific antibodies above the threshold specified by the manufacturer. In this sense, we report 56.0% (n=349/623) of seroconverted individuals. Relative seroconversion peaked after introduction of the Coronavac vaccine in February 2021. Vaccination increased the production of anti-S IgG from 3.9% to 48.6%. Our results also indicated that 11.0% (n=46/417) of all individuals were positive for TB. Seroconversion to SARS-CoV-2 was similar between individuals with positive tuberculosis test results to those with negative test results. Most vaccinated individuals seroconverted to SARS-CoV-2, indicating that Coronavac may be as protective in individuals from these indigenous groups as observed in the general Brazilian population. COVID-19 severity was minimal regardless of incomplete vaccine coverage, suggesting that vaccination may not be the only factor protecting individuals from severe COVID-19. Tuberculosis is highly prevalent and not associated with increased seroconversion to SARS-CoV-2.

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.

Subunit vaccines stand as a leading approach to expanding the current portfolio of vaccines to fight against COVID-19, seeking not only to lower costs but to achieve long-term immunity against variants of concern and have the main attributes that could overcome the limitations of the current vaccines. Herein a chimeric protein targeting S1 and S2 epitopes, called LTp50, was designed as a convenient approach to induce humoral responses against SARS-CoV-2. LTp50 was produced in recombinant Escherichia coli using a conventional pET vector, recovering the expected antigen in the insoluble fraction. LTp50 was purified by chromatography (purity > 90%). The solubilization and refolding stages helped to obtain a stable protein amenable for vaccine formulation. LTp50 was adsorbed onto alum, resulting in a stable formulation whose immunogenic properties were assessed in BALB/c mice. Significant humoral responses against the S protein (BA.5 variant) were detected in mice subjected to three subcutaneous doses (10 µg) of the LTp50/alum formulation. This study opens the path for the vaccine formulation optimization using additional adjuvants to advance in the development of a highly effective anti-COVID-19 vaccine directed against the antigenic regions of the S protein, which are less prone to mutations. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19, caused by SARS-CoV-2, has resulted in significant mortality and morbidity worldwide. Patients of chronic kidney disease who are on maintenance hemodialysis represent a vulnerable population cohort that is susceptible to severe disease. Hence, it is of utmost importance to prioritize vaccination in this population and to assess their response to said vaccination. Methods: This prospective analytical study was conducted at the Institute of Nephrology, Madras Medical College, between August 2021 and February 2022. Patients of chronic kidney disease stage 5 dialysis (CKD5D) who were on maintenance hemodialysis and who consented to receive COVID-19 vaccine were studied. Serum samples were obtained before vaccination, ≥28 days after receiving the first dose of the vaccine, and ≥28 days after receiving the second dose. Antibody titers against the spike protein were estimated using the Roche chemiluminescent immunosorbent assay. Patients were grouped into non-responders/seronegative (<0.8 U/ml) and responders/seropositive (≥0.8 U/ml), with a value ≥250 U/ml considered as robust response. Results: A total of 96 patients were included. The mean age was 36.70 (±11.53) years and 77.1% of them were male. The median dialysis vintage was 2 (IQR: 0.95-5) years. Twelve patients (9.9%) had a prior COVID-19 infection. Sixty-seven (69.8%) patients had received Covaxin and 29 (30.2%) had received Covishield vaccines. Among the 17 patients who were seronegative at baseline, 4 (23.52%) became seropositive after the first dose of the vaccine, and 11 (64.7%) were seropositive after the second dose, with high titers ("robust response") achieved in two patients (11.76%). No antibody response, despite two doses of the vaccine, was noted in six patients (35.29%). Conclusion: Our study showed a high baseline seropositivity rate, even prior to vaccination, which indicated a high rate of subclinical COVID infection. Among those who were seronegative at baseline, the seroconversion rate after two doses of Covaxin or Covishield was 64.70%. [ABSTRACT FROM AUTHOR]

Background Waning immunity after the coronavirus disease 2019 (COVID-19) vaccinations creates the constant need of boosters. Predicting individual responses to booster vaccines can help in its timely administration. We hypothesized that the humoral response to the first two doses of the BNT162b2 vaccine can predict the response to the booster vaccine. Methods A prospective cohort of hospital health care workers (HCW) that received three doses of the BNT162b2 vaccine. Participants completed serological tests at 1 and 6 months after the second vaccine dose and 1 month after the third. We analyzed predictive factors of antibody levels after the booster using multivariate regression analyses. Results From 289 eligible HCW, 89 (31%) completed the follow-up. Mean age was 48 (±10) and 46 (52%) had daily interaction with patients. The mean (±standard deviation) antibody level 1 month after the second vaccine was 223 (±59) AU/ml, and 31 (35%) had a rapid antibody decline (>50%) in 6 months. Low antibody levels 1 month after the second vaccine and a rapid antibody decline were independent predictors of low antibody levels after the booster vaccine. Conclusions The characteristics of the humoral response to COVID-19 vaccinations show promise in predicting the humoral response to the booster vaccines. [ABSTRACT FROM AUTHOR]

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation. [ABSTRACT FROM AUTHOR]

We investigated humoral and T-cell response to a SARS-CoV-2 mRNA vaccine in solid organ transplant recipients (SOT-Rs) and healthy donors (HDs) before (T0) and after two (T1) and twelve months (T2) since the third dose administration. SOT-Rs were stratified according to the transplanted organ and to the time elapsed since the transplant. In SOT-Rs, detectable levels of anti-S antibodies were observed in 44%, 81% and 88% at T0, T1 and T2, respectively. Conversely, anti-S antibody levels were detected in 100% of HD at all time points. Lower antibody titers were observed in SOT-Rs compared to HDs, even stratifying by transplanted organs and the time elapsed since transplant. Lower percentages of responding and polyfunctional T-cells were observed in SOT-Rs as well as in each subgroup of SOT-Rs compared to HDs. At both T0 and T1, in SOT-Rs, a predominance of one cytokine production shortly was observed. Conversely, at T2, a dynamic change in the T-cells subset distribution was observed, similar to what was observed in HDs. In SOT-Rs, the third dose increased the rate of seroconversion, although anti-S levels remained lower compared to HDs, and a qualitatively inferior T-cell response to vaccination was observed. Vaccine effectiveness in SOT-Rs is still suboptimal and might be improved by booster doses and prophylactic strategies. [ABSTRACT FROM AUTHOR]

The role of retroviral envelope proteins belonging to the Human Endogenous Retroviral family 'W' (HERV‐W), specifically syncytin‐1 and pathogenic HERV‐W (pHERV‐W), as potential risk factors in multiple sclerosis (MS) has been established. This study aimed to investigate the humoral response to syncytin‐1 and pHERV‐W‐derived peptides in a group of relapsing remitting MS patients categorized as having acute or stable disease. Furthermore, an inhibition assay was conducted to assess the extent of cross‐reactivity between the two epitopes. The findings revealed that MS patients in the acute phase exhibited a higher specific antibody response to the pHERV‐W env epitope compared to syncytin‐1. This suggests a potential pathogenic role for pHERV‐W env during the inflammatory stages of central nervous system involvement, and these antibody responses could serve as useful biomarkers for monitoring the progression of the disease. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluated the immune response to a multiepitope recombinant chimeric protein (CHIVAX) containing B- and T-cell epitopes of the SARS-CoV-2 spike's receptor binding domain (RBD) in a translational porcine model for pre-clinical studies. Methods: We generated a multiepitope recombinant protein engineered to include six coding conserved epitopes from the RBD domain of the SARSCoV-2 S protein. Pigs were divided into groups and immunized with different doses of the protein, with serum samples collected over time to determine antibody responses by indirect ELISA and antibody titration. Peptide recognition was also analyzed by Western blotting. A surrogate neutralization assay with recombinant ACE2 and RBDs was performed. Intranasal doses of the immunogen were also prepared and tested on Vietnamese minipigs. Results: When the immunogen was administered subcutaneously, it induced specific IgG antibodies in pigs, and higher doses correlated with higher antibody levels. Antibodies from immunized pigs recognized individual peptides in the multiepitope vaccine and inhibited RBD-ACE2 binding for five variants of concern (VOC). Comparative antigen delivery methods showed that both, subcutaneous and combined subcutaneous/intranasal approaches, induced specific IgG and IgA antibodies, with the subcutaneous approach having superior neutralizing activity. CHIVAX elicited systemic immunity, evidenced by specific IgG antibodies in the serum, and local mucosal immunity, indicated by IgA antibodies in saliva, nasal, and bronchoalveolar lavage secretions. Importantly, these antibodies demonstrated neutralizing activity against SARSCoV-2 in vitro. Discussion: The elicited antibodies recognized individual epitopes on the chimeric protein and demonstrated the capacity to block RBD-ACE2 binding of the ancestral SARS-CoV-2 strain and four VOCs. The findings provide proof of concept for using multiepitope recombinant antigens and a combined immunization protocol to induce a neutralizing immune response against SARS-CoV-2 in the pig translational model for preclinical studies. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is an antibody-mediated autoimmune neurological disorder characterized by impaired neuromuscular junction transmission, resulting in muscle weakness. Recently, the involvement of Human Endogenous Retroviruses (HERVs) in the pathophysiology of different immune-mediated and neurodegenerative diseases, such as multiple sclerosis, has been demonstrated. We aimed to investigate potential immune system involvement related to humoral responses targeting specific epitopes of HERV-K and HERV-W envelope proteins in myasthenia gravis. Myasthenia gravis patients were recruited in the Neurology Unit, while healthy controls were selected from the Blood Transfusion Center, both affiliated with AOU Sassari. Highly immunogenic antigens of HERV-K and HERV-W envelope proteins were identified using the Immune Epitope Database (IEDB) online tool. These epitopes were utilized in enzyme-linked immunosorbent assays (ELISA) to detect autoantibodies in serum directed against these sequences. The study involved 39 Healthy Donors and 47 MG patients, further categorized into subgroups based on the presence of autoantibodies: MG-AchR Ab+ (n = 17), MG-MuSK Ab+ (n = 7), double seronegative patients (MG-DSN, n = 18), MG-LRP4 Ab + (n = 4), and one patient with no antibodies data (n = 1). Our findings revealed high levels of autoantibodies in myasthenia gravis patients directed against the HERV-K-env-su(19–37), HERV-K-env-su(109–126), HERV-K-env-su(164–186), HERV-W-env(93–108), HERV-W-env(129–14), and HERV-W-env(248–262) epitopes. Notably, these results remained highly significant even when patients were subdivided into MG-AchR Ab+ and MG-DSN subgroups. Correlation analysis further revealed significant positive associations between the antibody levels against HERV-K and HERV-W families in patients, suggesting a synergistic action of the two HERVs in the pathology context since this correlation is absent in the control group. This study marks the first identification of a specific humoral response directed against defined epitopes of HERV-K and HERV-W envelope proteins in myasthenia gravis patients. These findings lay the foundation for future investigations aimed at elucidating the molecular mechanisms driving this immune response. The detection of these autoantibodies suggests the potential for novel biomarkers, especially within the MG-DSN patient subgroup, addressing the need for new biomarkers in this population. [ABSTRACT FROM AUTHOR]

Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Blood samples were collected before the administration of the bivalent booster from Pfizer‐BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma from T cells in response to an in vitro SARS‐CoV‐2 stimulation. A substantial waning of neutralizing antibodies was observed after 6 months (23.1‐fold decrease), especially considering the XBB.1.5 subvariant. The estimated T1/2 of neutralizing antibodies was 16.1 days (95% CI = 10.2–38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.95 vs. 0.41 UI/L, p = 0.0083). A significant waning of the humoral and cellular response was observed after 6 months. These data can also help competent national authorities in their recommendation regarding the administration of an additional booster. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RP) remains a difficult-totreat disease of unknown aetiology and uncertain prognosis. Based on McAdam's criteria, rheumatoid arthritis (RA) was diagnosed in a 51-year-old female patient, and sequential therapy with dapsone -- followed by naproxen and methylprednisolone -- was initiated without achieving full remission. During the following years, the patient developed new locations of polychondritis (nose, epiphyses of long bones) and episcleritis. Methotrexate (MTX) was started, which was changed to mycophenolate mofetil (MM) due to adverse effects, resulting in sustained clinical improvement. There were no relapses during the subsequent 12 months of follow-up. The use of MM with good therapeutic effect in our patient is one of the few reported cases of such therapy in a patient with RP. [ABSTRACT FROM AUTHOR]

IntroductionAntibody production and the generation of memory B cells are regulated by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in germinal centers. However, the precise role of Tfr cells in controlling antibody production is still unclear. We have previously shown that both Tfh and Tfr cells express the IL-1R1 agonist receptor, whereas only Tfr cells express the IL-1R2 decoy and IL-1Ra antagonist receptors. We aimed to investigate the role of IL-1 receptors in the regulation of B cell responses by Tfh and Tfr.MethodsWe generated mice with IL-1 receptors inactivated in Tfh or Tfr and measured antibody production and cell activation after immunisation.ResultsWhile IL-1β levels are increased in the draining lymph node after immunisation, antigen-specific antibody levels and cell phenotypes indicated that IL-1β can activate both Tfh and Tfr cells through IL-1R1 stimulation. Surprisingly, expression of IL-1R2 and IL-1Ra on Tfr cells does not block IL-1 activation of Tfh cells, but rather prevents IL-1/IL-1R1-mediated early activation of Tfr cells. IL-1Rs also regulate the antibody response to autoantigens and its associated pathophysiology in an experimental lupus model.DiscussionCollectively, our results show that IL-1 inhibitory receptors expressed by Tfr cells prevent their own activation and suppressive function, thus licensing IL-1-mediated activation of Tfh cells after immunisation. Further mechanistic studies should unravel these complex interactions between IL-1β and follicular helper and regulatory T cells and provide new avenues for therapeutic intervention.

Abstract The role of follicular T helper (Tfh) cells in humoral response has been considered essential in recent years. Understanding how Tfh cells control complex humoral immunity is critical to developing strategies to improve the efficacy of vaccines against SARS-CoV-2 and other emerging pathogens. However, the immunologic mechanism of Tfh cells in SARS-CoV-2 receptor binding domain (RBD) vaccine strategy is limited. In this study, we expressed and purified recombinant SARS-CoV-2 RBD protein in Drosophila S2 cells for the first time and explored the mechanism of Tfh cells induced by RBD vaccine in humoral immune response. We mapped the dynamic of Tfh cell in lymph node and spleen following RBD vaccination and revealed the relationship between Tfh cells and humoral immune response induced by SARS-CoV-2 RBD vaccine through correlation analysis, blocking of IL-21 signaling pathway, and co-culture of Tfh with memory B cells. Recombinant RBD protein elicited a predominant Tfh1 and Tfh1-17 subset response and strong GC responses in spleen and lymph nodes, especially to enhanced vaccination. IL-21 secreted by Tfh cells affected the development and differentiation of B cells and played a key role in the humoral immune response. These observations will help us further understand the mechanism of protective immune response induced by COVID-19 vaccine and has guiding significance for the development of vaccines against newly emerging mutants.

Fourth dose of SARS-CoV-2 vaccination was started from the end of May, 2022 in Japan. However, data on the precise analysis of the side effects after fourth vaccination, remain scarce. Here, we examined the side effects and the levels of SARS-CoV-2 antibody titers in healthy volunteers who underwent BNT162b2 vaccination for the fourth time.

Background: Vaccination is one of the most effective medical interventions to prevent infectious diseases. The introduction of vaccines against coronavirus acute respiratory syndrome 2 (SARS-CoV-2) was aimed at preventing severe illness and death due to coronavirus disease 2019 (COVID-19). Solid organ transplant recipients (SOTRs) are at high risk of infection with SARS-CoV-2 and serious effects associated with COVID-19, mainly due to the use of immunosuppressive therapies, which further cause suboptimal response to COVID-19 vaccination. Aim of the study: We aimed to compare post-vaccination response to BNT162b2 in kidney–pancreas transplant recipient, specifically in immunocompetent individuals, over two years of simultaneous monitoring. Methods: To determine the humoral response, the levels of the IgG and IgA anti-S1 antibodies were measured. To assess the cellular response to SARS-CoV-2, the released IFN-γ-S1 was determinate. Results and Conclusion: After primary vaccination, compared to immunocompetent subjects, SOTR showed lower seroconversion for both antibody classes. Only the additional dose produced antibodies at the level reached by the control group after the baseline vaccination. During the monitored period, SOTR did not achieve a positive cellular response in contrast to immunocompetent individuals, so in order to obtain longer protection, including immune memory, the adoption of booster doses of the vaccine should be considered.

We recently showed that an adapted SARS-CoV-2 vaccine with wildtype and BA.4/BA.5 Omicron subtype epitopes induced a broad short-term immune response in hemodialysis patients. Antibodies with protective capacity were boosted significantly after a follow-up period of 3 weeks following a fifth vaccine dose. However, data on the longevity of the humoral response after bivalent vaccination are lacking but urgently needed to make recommendations for further booster vaccinations in this patient group. This study is an extension of our previously published data including 40 patients on hemodialysis with a follow-up period of 12 months after an adapted booster vaccine dose. We performed a detailed characterization of humoral immune responses and assessed breakthrough infections. In addition, the severity of breakthrough infections was assessed using an established grading system. Anti-S1 IgG and surrogate neutralizing antibodies significantly decreased during the period of 12 months (p < 0.01 and p < 0.001, respectively). Live-virus neutralizing antibodies against the wildtype and the BA.5 subtype also significantly decreased over time (p < 0.01 and p < 0.01, respectively). However, even 12 months after administration of the adapted vaccine dose, all 40/40 (100%) of hemodialysis patients showed detectable SARS-CoV-2 wildtype neutralization activity, with 35/40 (88%) also exhibiting detectable BA.5 subtype neutralization activity. During follow-up, 13/40 (33%) patients contracted a SARS-CoV-2 breakthrough infection, among which 12 cases were categorized as asymptomatic or mild, while only 1 case was classified as moderate disease activity. Thus, bivalent booster vaccination seems to induce a sustained immune response in hemodialysis patients over a period of 12 months with breakthrough infections occurring frequently but predominantly manifesting as asymptomatic or mild.

HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity.

Abstract The aim of the study was to evaluate the association between salivary anti-Porphyromonas gingivalis IgA antibodies and the leprosy reaction. The levels of salivary anti - P. gingivalis IgA antibodies, together with salivary flow and pH were measured in individuals diagnosed with leprosy and associated with the development of the leprosy reaction. Saliva was collected from 202 individuals diagnosed with leprosy at a reference leprosy treatment center, 106 cases with the leprosy reaction and 96 controls without the leprosy reaction. Anti - P. gingivalis IgA was evaluated by indirect immunoenzyme assay. Non-conditional logistic regression analysis was employed to estimate the association between antibody levels and the leprosy reaction. There was a positive statistically significant association between the levels of anti - P. gingivalis IgA and the presence of the leprosy reaction, controlling for confounders: age, sex, level of education and alcoholic beverage consumption: ORajusted: 2.55; IC 95%: 1.34–4.87. Individuals with leprosy who had high levels of salivary anti - P. gingivalis IgA had approximately twice as many chances of developing the leprosy reaction. The findings suggest a possible relationship between salivary anti - P. gingivalis IgA antibodies and the leprosy reaction.

Introduction: The development of innovative anti-COVID-19 vaccines is a need to ensure the population’s immunity worldwide, with broad protection against variants of concern and low cost as the main goals. Gold nanocarriers are potential entities that could aid in the development of innovative vaccines having thermal stability, high immunogenicity, and safety as the main attributes. Moreover, this approach could lead to adjuvant-free formulations, which will reduce the costs of vaccines.Methods: In this study, five peptides (P1, P2, P3, P4, and P5) corresponding to linear epitopes of the SARS-CoV-2 spike (S) protein were chemisorbed on gold nanoparticles (AuNP) of 20 nm, prefunctionalized with heterobifunctional polyethylene glycol, by using glutaraldehyde as crosslinker to generate nanovaccine prototypes.Results and discussion: The surface modification was confirmed by DLS with an increase of 31.7 ± 1.8 nm in the hydrodynamic diameter and an average ζ potential of −8.3 ± 2.2 mV in PBS (as excipient). The coupling concentration achieved was 23.7 ± 7.1 μg of peptide per mg AuNP. These AuNP-based conjugates showed no inherent toxicity in assays performed with HEK293T cells, in which a 100–1,000 μg/mL concentration range only led to a temporary decrease of up to 30% in cell viability after 48 h of treatment with restoration by 72 h. The immunogenicity of the conjugates produced was assessed in test mice subjected to three subcutaneous doses at 2-week intervals. Significant levels of IgM against each target peptide were observed at an early stage of the immunization scheme in all groups, reaching maximum levels after the second dose, whereas the IgG response increased after the third dose. The AuNP-P2, AuNP-P3, and AuNP-P5 conjugates induced the highest levels of IgG antibodies, lasting for at least 2 months after the last boost, with a predominance of the IgG1 subclass. Although the magnitude of the response induced by the gold conjugates was comparable to that with alum as adjuvant, these nanoconjugates induced a longer response. Our data support the use of AuNP as carriers in innovative vaccines against SARS-CoV-2.