Vaccine-specific Antibody Research Articles

Antibody Persistence and Risk of COVID-19 Infection: Insights from Modeling.

In this post hoc exploratory study of the APHP-COVIBOOST trial (NCT05124171), we used statistical modeling to describe the evolution of neutralizing antibody (nAb) titers over time, asses its impact on SARS-CoV-2 infection, and explore potential differences between three booster vaccine formulations (D614, B.1.351, and BNT162b2). Antibody titers were measured for 208 adult participants at day 28, 3 months, and 6 months using a microneutralization assay against different Omicron subvariants. We developed four specific Bayesian statistical models based on a core model, accounting for vaccine-specific antibody decline, boosting of nAb for breakthrough infection, and risk of infection according to nAb levels. The model findings were cross-verified using another validated microneutralization assay. The decrease in nAb titers was significantly lower for the B.1.351 vaccine than for the other booster formulations. An inverse relationship was found between risk of infection upon exposure and nAb levels. With Omicron BA.1 data, these results translated into a positive relative vaccine efficacy against any infection over 6 months for the B.1.351 vaccine compared to the BNT162b2 (31%) and D614 (21%) vaccines. Risk of infection decreased with increasing nAb titers for all vaccines. Statistical models predicted significantly better antibody persistence for the B.1.351 booster formulation compared to the other evaluated vaccines.

A Serum Multi-Parametric Analysis Identifies an Early Innate Immune Signature Associated to Increased Vaccine-Specific Antibody Production and Seroconversion in Simultaneous COVID-19 mRNA and Cell-Based Quadrivalent Influenza Vaccination.

In this pilot study, a multi-parametric analysis comparing immune responses in sera of adult healthy subjects (HS) or people with type 2 diabetes mellitus (T2D) undergoing the single or simultaneous administration of mRNA-based COVID-19 and cellular quadrivalent inactivated influenza vaccines was conducted. While SARS-CoV-2 antibodies remains comparable, influenza antibody titers and seroconversion were significantly higher upon simultaneous vaccination. Magnitude of anti-influenza humoral response closely correlated with an early innate immune signature, previously described for the COVID-19 vaccine, composed of IL-15, IL-6, TNF-α, IFN-γ, CXCL-10 and here extended also to acute-phase protein Pentraxin 3. People with T2D receiving simultaneous vaccination showed a protective response comparable to HS correlating with the early induction of IFN-γ/CXCL10 and a significant reduction of the circulating glucose level due to increased oxidation of glucose digestion and consumption. These data, although preliminary and in-need of validation in larger cohorts, might be exploited to optimize future vaccination in people with chronic disorders, including diabetes.

The Major Role of T Regulatory Cells in the Efficiency of Vaccination in General and Immunocompromised Populations: A Review.

Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells (T cytotoxic; Tc), as well as B cell (BIgM, BIgG, BIgA and BIgE) subsets, during the response to vaccination. Both T and B cell subsets form central, peripheral, and tissue-resident subsets during vaccination. It has also become apparent that each vaccination forms a network of T regulatory subsets, namely CD4+ CD25+ Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+ Foxp3- T regulatory 1 (Tr1), as well as many others, which shape the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on considering how the pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work has revealed that Treg/Tr1 involvement evokes different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response, such as increasing the dose, changing the delivery route, and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Rα chain) or anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAb) to decrease the Tregs and boost the T/B cell immune response. All of these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals, as well as organ transplant patients.

Seroprevalence of Measles (Rubeola) Antibodies in Childhood Cancer Survivors.

Background: Measles is reemerging as a public health threat, raising important questions about disease vulnerability among childhood cancer survivors. This secondary analysis assessed the seroprevalence of anti-measles immunoglobulin G (IgG) antibodies as a marker of immune status in survivors of childhood cancer and associated demographic/treatment variables. Method: Participants were childhood cancer survivors who were free of active disease, having routine blood studies drawn, and could provide documentation of having received two doses of measles, mumps, and rubella vaccine before their cancer diagnosis. Patient record review documented demographic and treatment variables. Antimeasles (rubeola) IgG antibody seroprevalence was assessed by enzyme immunoassay for vaccine-specific antibodies. Results: Of 270 survivors evaluated, 110 (42%) were female, 196 (75%) were White, and 159 (61%) were leukemia/lymphoma survivors. Of these 262, 110 (42%) had negative measles seroprevalence, suggesting loss of immunity. Conclusion: Measles antibody surveillance and the need for reimmunization for survivors of childhood cancer survivors outside the transplant setting remains controversial. Our analysis indicates that a substantial proportion of survivors lose vaccine-related immunity to measles. Pediatric oncology nurses play important roles in educating cancer survivors regarding their risk of measles infection, evaluating the need for reimmunization, correcting misinformation about vaccine safety and effectiveness, and working to optimize community herd-based immunity.

Sex Differences in Exercise-Induced Modulation of the Humoral Immune Response to Influenza Vaccination

Physical activity is known to modulate immune cell function and understanding its role in vaccine-induced immunity is critical for both optimizing vaccine strategies and implementing lifestyle factors that contribute to better immune health. This study aimed to elucidate the impact of physical activity on antibody responses following influenza vaccination, with a specific focus on biological sex differences among male and female cross-country athletes. Based on previous studies, we hypothesized that physical activity would increase immune responses, regardless of biological sex. Two cohorts of male and female Division III college cross-country runners and two cohorts of non-athletes (no physical activity) participated in this longitudinal investigation. Studies were conducted in two separate influenza seasons where participants received a quadrivalent seasonal influenza vaccine (2020-21 and 2022-23). An estimated non-adjusted VO2 max was calculated, and a survey was administered to identify overall health status prior to the start of the study. Blood samples were collected at predefined intervals to assess pre- and post-vaccination antibody responses specific for the H1N1 component of each seasonal influenza vaccine. VO2 max, a measure of overall fitness, was higher in the athletes as compared to those participants who were not physically active, and these results were consistent among both males and females. All participants mounted an immune response to the seasonal influenza vaccine as indicated by a rise in vaccine-specific antibody titers from pre-vaccination to post-vaccination. However, the differences in titers were sex specific, with greater neutralizing antibody titers in females as compared to males — regardless of their level of physical activity. When data were further partitioned by physical activity level, it was identified that although males have lower antibody responses than females, males that were cross country runners had significantly greater antibody responses than males that were not physically active. This study contributes valuable insights into the complex interplay between exercise, sex, and immune responses. Understanding these dynamics could inform recommendations for individuals to be engaged in regular physical activity to optimize overall immune health. This research was funded by a College of Saint Benedict and Saint John's University Faculty Development and Research Committee Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Supplementation of seasonal vaccine with multi-subtype neuraminidase and M2 ectodomain virus-like particle improves protection against homologous and heterologous influenza viruses in aged mice

The conventional inactivated split seasonal influenza vaccine offers low efficacy, particularly in the elderly and against antigenic variants. Here, to improve the efficacy of seasonal vaccination for the elderly population, we tested whether supplementing seasonal bivalent (H1N1 + H3N2) split (S) vaccine with M2 ectodomain repeat and multi-subtype consensus neuraminidase (NA) proteins (N1 NA + N2 NA + flu B NA) on a virus-like particle (NA-M2e) would induce enhanced cross-protection against different influenza viruses in aged mice. Immunization with split vaccine plus NA-M2e (S + NA-M2e) increased vaccine-specific IgG antibodies towards T-helper type 1 responses and hemagglutination inhibition titers. Aged mice with NA-M2e supplemented vaccination were protected against homologous and heterologous viruses at higher efficacies, as evidenced by preventing weight loss, lowering lung viral loads, inducing broadly cross-protective humoral immunity, and IFN-γ+ CD4 and CD8 T cell responses than those with seasonal vaccine. Overall, this study supports a new strategy of NA-M2e supplemented vaccination to enhance protection against homologous and antigenically different viruses in the elderly.

Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine.

The house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented in clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) represents a significant progression of recombinant hypoallergenic allergen derivatives. The three-dimensional protein structure of Der f 36 was constructed using Alphafold2. AI-based tools were employed to predict B-cell epitopes, which were subsequently verified through IgE-reaction testing. Hypoallergenic Der f 36 was then synthesized, expressed, and purified. The reduced allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and basophil activation test. T-cell response to hypoallergenic Der f 36 and Der f 36 was evaluated based on cytokine expression in the peripheral blood mononuclear cells (PBMCs) of patients. The immunogenicity was evaluated and compared through rabbit immunization with hypoallergenic Der f 36 and Der f 36, respectively. The inhibitory effect of the blocking IgG antibody on the specific IgE-binding activity and basophil activation of Der f 36 allergen was also examined. The final selected non-allergic B-cell epitopes were 25-48, 57-67, 107-112, 142-151, and 176-184. Hypoallergenic Der f 36 showed significant reduction in IgE-binding activity. The competitive inhibition of IgE-binding to Der f 36 was investigated using the hypoallergenic Der f 36, and only 20% inhibition could be achieved, which is greatly reduced when compared with inhibition by Der f 36 (98%). The hypoallergenic Der f 36 exhibited a low basophil-stimulating ratio similar to that of the negative control, and it could induce an increasing level of IFN-γ but not Th2 cytokines IL-5 and IL-13 in PBMCs. The vaccine-specific rabbit blocking IgG antibodies could inhibit the patients' IgE binding and basophil stimulation activity of Derf 36. This study represents the first application of an AI strategy to facilitate the development of a B-cell epitope-based hypoallergenic Der f 36 vaccine, which may become a promising immunotherapy for HDM-allergic patients due to its reduced allergenicity and its high immunogenicity in inducing blocking of IgG.

NVX-CoV2373 induces humoral and cellular immune responses that are functionally comparable to vector and mRNA-based vaccines.

After licensing of the protein-based vaccine NVX-CoV2373, three technically different vaccines against the SARS-CoV-2 became available for application to the human population - and for comparison of efficacies. We here recruited 42 study participants who had obtained one initial dose of NVX-CoV2373 and analyzed their immune responses in contrast to 37 study participants who had obtained either the vector vaccine AZD1222 or the mRNA vaccine BNT162b2 a year earlier. 32 participants also donated blood before first vaccination to serve as a vaccine-naive control. In detail, we investigated and quantified at day 21 and approximately six months after primary immunization the amounts of vaccine-specific antibodies produced, their neutralization capacity, their quality in terms of binding different epitopes and their efficiency in inducing various isotypes. Cellular immunity and intracellular cytokine production following in vitro re-stimulation with BNT162b2 vaccine was analyzed via ELISpot or via flow cytometry. Our results show that even though vaccination including the mRNA vaccine yielded best results in almost any aspect of antibody levels and binding efficiency, the neutralization capacities against the wild-type Wuhan strain and the Omicron BA.1 variant early and at six months were comparable among all three vaccination groups. As for the T cells, we observed a prevailing CD8 response at three weeks which turned into a predominant CD4 memory at six months which has not yet been observed for AZD1222 and BNT162b2. While additional infection with SARS-CoV-2 resulted in a boost for the humoral response, T cell memory appeared rather unaffected. Whether any of these differences translate into real world protection from infection, mitigation of severe disease courses and prevention of long/post COVID will need to be investigated in the future.

The Effects of Dairy Consumption on Vaccine Immune Response and Immunoglobulins: A Systematic Literature Review

Public health interest in vaccinations and immune protection has increased with the COVID-19 pandemic. Dairy products are an important source of protein and other nutrients, and there are unresolved research questions regarding the potential health impact of dairy products on the enhancement of immune response. A systematic literature review was conducted to synthesize the published literature reporting the effects of dairy interventions on: 1) the vaccine-specific immune response and 2) immunoglobulins in the absence of vaccination. To assess study validity and quality, we used the Academy of Nutrition and Dietetics Quality Criteria Checklist. Sixty-one studies (59 clinical trials, 1 cohort, 1 cross-sectional survey) were included, spanning 1983-2017. Ten trials evaluated the effect of dairy intervention on vaccine-specific IgG, IgA, IgM, vaccine-specific antibody titers, seroprotection rates, or seroconversion rates. Of these, 7 reported significant increases with dairy interventions for post-vaccine tetanus antibodies, mean change in tetanus antibody level, total antibody titers to flagellin from Salmonella Adelaide, mean antibody titers to influenza B, influenza-specific IgA and IgG levels, and seroconversion or seroprotection rates for influenza A and B. Fifty-six studies evaluated dairy’s effects on immunoglobulins without vaccinations. The results were heterogenous, with some studies reporting significant enhancement of immunoglobulins (IgA, IgE, or IgG), while others observed no differences between groups. Clinical relevance of the immunoglobulin changes was not investigated in these studies. Dairy products and their components could enhance the efficacy of vaccines. This review highlights the evidence gaps and provides a potential roadmap for additional research.

Clinical and immunological outcomes of HIV-exposed uninfected and HIV-unexposed uninfected children in the first 24months of life in Western Kenya.

Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24months of life. Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

High-resolution snapshots of antibody repertoires as potential correlates of protection

High-resolution snapshots of antibody repertoires as potential correlates of protection Klaus Eyer from ETH Zurich describes high-resolution snapshots of antibody repertoires as potential correlates of protection. The induction and long-term presence of key adaptive immune cells are essential for vaccine-mediated protection. As a direct, causal measure of protection is often challenging; finding and defining correlates of protection are critical for vaccine development, approval, and efficacy testing. Correlates of protection are quantifiable signs of being protected from becoming infected and/or developing disease that may be causal to protection itself. Antibodies in serum are often assessed as potential correlates as immunisations often lead to generating a vaccine-specific, functionally active and diverse antibody repertoire. In its simplest form, a potential correlate could be their presence if binding by the antibody is sufficient. This is assessed in the so-called titer measurements. Here, a serum sample is sequentially diluted, and the binding of the antibodies towards the vaccine is evaluated and compared to an often empirically derived threshold. This gold-standard measure has many advantages: it is fast, reliable and easily compared.

A Prospective Study of Seroconversion Post Covishield Vaccination in COVID-19 Warriors

Introduction: During the Coronavirus Disease 2019 (COVID19) pandemic in India, two vaccinees were predominantly administered to prevent the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The first vaccine introduced in India was ChAdOx1-nCOV (Covishield), followed by BBV-152 (Covaxin). In the first phase, Healthcare Workers (HCW) were prioritised for vaccination, given their crucial role in the healthcare system. Aim: To assess the antibody response post Covishield vaccination at specific time intervals in HCWs and to determine the correlation of antibody response with age, gender, comorbidities and blood group. Materials and Methods: This prospective study was conducted at Dr. Balasaheb Vikhe Patil Rural Medical College, Pravara Institute of Medical Sciences, Loni, Maharashtra, India, over a duration of six months from January 2021 to June 2021. A total of 110 vaccinated HCWs who volunteered were included in this study. SARS-CoV-2 antibodies at specific time intervals were assessed using Ortho Clinical Diagnostic’s VITROS 3600 based on the principle of Chemiluminescent Immunosorbent Assay (CLIA). Assessment of anti-SARS-CoV-2 total and IgG antibodies was performed at 15 days, one month, one and a half months, two months, three months, and four months postfirst dose of vaccination, or in other words, 15 days and one month after the 1st dose, and 15 days, one month, two months, and three months post second dose of vaccination. For analysis, Pearson’s correlation and a regression model were performed using GraphPad Prism 8.0.2 version. Results: Fifteen days post second dose, 110 HCWs (100%) and 109 (99.09%) HCWs turned seropositive for total antibodies and IgG antibodies, respectively. It was observed that the majority of participants (33, 30.27%) with peak IgG levels in the medium range were from the age group of 31-40 years. Overall, there was a negative correlation between age and IgG antibody levels for peak IgG values (r-value=-0.224, p-value=0.019). The peak values were achieved in the majority of participants 15 days post second dose (53.6%). The difference in antibody levels based on gender was not significant (Chi-square value=3.387, p-value=0.184). No significant difference in SARS-CoV-2 IgG levels was observed between participants with co-morbidities and those without co-morbidities. Participants who developed SARS-CoV-2 infection during the study period exhibited robust antibody responses after vaccination. Conclusion: These findings help elucidate Covishield vaccinespecific antibody responses in vaccinees of different age groups, genders, blood groups, and with co-morbid conditions. The vaccine has substantially reduced the burden of disease by preventing serious illness in vaccinated HCWs during the second wave of the COVID-19 pandemic.

Early-life exposure to perfluoroalkyl substances and serum antibody concentrations towards common childhood vaccines in 18-month-old children in the Odense Child Cohort

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with reduced antibody response to childhood vaccinations. Previous studies have mostly focused on antibodies against diphtheria or tetanus, while fewer studies have assessed antibodies toward attenuated viruses, such as measles, mumps or rubella (MMR). Therefore, we set out to determine associations between prenatal and early postnatal PFAS exposure and vaccine-specific Immunoglobulin G (IgG) in the background-exposed Odense Child Cohort. Blood samples were drawn in pregnancy at gestation weeks 8–16 and from the offspring at age 18 months. In the maternal serum samples we quantified perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). In the offspring serum samples we quantified the same five PFAS compounds and IgG towards diphtheria, tetanus and MMR. A total of 880 and 841 children were included in the analyses of diphtheria and tetanus or MMR, respectively. Multiple linear regression models were used for estimation of difference in virus-specific IgG per doubling of PFAS concentrations. Maternal PFAS concentrations were non-significantly inversely associated with most vaccine-specific antibody concentrations. Likewise, child PFAS concentrations were associated with non-significant reductions of antibodies towards tetanus and MMR. A significant reduction in the percent difference in mumps antibody concentration per doubling of child PFNA (−9.2% (95% confidence interval: −17.4;-0.2)), PFHxS (−8.3% (−15.0;-1.0) and PFOS (−7.9% (−14.8;-0.4) was found. These findings are of public health concern, as inadequate response towards childhood vaccines may represent a more general immune dysfunction.

Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors.

Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known. RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skåne University Hospital, Lund and Malmö, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed. Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a ≥4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination. The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population. ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038.

Maternal Immunization During the Second Trimester with BNT162b2 mRNA Vaccine Induces a Robust IgA Response in Human Milk: A Prospective Cohort Study

BackgroundThe human milk antibody response following maternal immunization with the BNT162b2 mRNA vaccine is important for the protection of the infant during infancy. The vaccine-specific antibody response is still unclear at different stages of human milk production, as are the effects of maternal immunization timing on the robustness of the antibody response. ObjectivesThe study aimed to assess the antibody response (IgG/IgA/IgM) during various lactation stages and identify the best vaccination timing during pregnancy. MethodsA prospective cohort study of 73 postpartum women who were administered the BNT162b2 COVID-19 mRNA vaccine during the second or third trimester of pregnancy were recruited. Statistical comparison was conducted using 16 human milk samples from a prepandemic control group. ResultsExcluding 11 women, the study included 62 lactating women who were administered the mRNA vaccine during the second or third trimester of pregnancy. A total of 149 samples of human milk were collected at different lactation stages. Our findings reveal that colostrum exhibits significantly higher levels of IgG (95% confidence interval [CI]: 1.3, 9.0; P = 0.023), IgA (95% CI: 55.98, 100.2; P = 0.0034), and IgM (95% CI: 0.03, 0.62; P < 0.0001) compared with mature milk IgG (95% CI: 0.25, 0.43), IgA (95% CI: 9.65, 13.74), IgM (95% CI: 0.03, 0.04). The timing of maternal immunization affected the antibody response. The level of IgA in mature milk was higher when immunization occurred in the second trimester (95% CI: 11.14, 19.66; P = 0.006) than in the third trimester (95% CI: 7.16, 11.49). Conversely, IgG levels in mature milk were higher when immunization occurred during the third trimester (95% CI: 0.36, 0.65; P < 0.0001) than in the second trimester (95% CI: 0.09, 0.38). ConclusionsOur study provides evidence that administering the mRNA vaccine to pregnant women during the second trimester increases vaccine-specific IgA levels during lactation. Considering the significance of human milk IgA in mucosal tissues and its prevalence throughout lactation, it is reasonable to recommend maternal immunization with the BNT162b2 mRNA vaccine during the second trimester.This trial was registered at the Helsinki Committee of the Tel Aviv Medical Center as clinical trial number 0172-TLV.

Obesity accelerates age defects in B cells, and weight loss improves B cell function

BackgroundWe have previously shown that obesity accelerates age-associated defects in B cell function and antibody production leading to decreased secretion of protective antibodies and increased autoimmunity. We wanted to evaluate if obese adults enrolled in a voluntary weight reduction program had higher protective and lower autoimmune antibody responses similar to those observed in lean adults.MethodsExperiments were performed using blood isolated from an established cohort of female lean adult and elderly individuals, as well as from the blood of female adults with obesity, before and after a voluntary weight reduction program in which their Body Mass Index (BMI) was reduced 10–34% in 12 months. All participants were vaccinated with the Trivalent Inactivated Influenza vaccine. Serum samples were evaluated for the presence of pro-inflammatory cytokines and adipokines, vaccine-specific antibodies and autoimmune antibodies. We evaluated the composition of the B cell pool by flow cytometry, the expression of RNA for class switch transcription factors and pro-inflammatory markers by qPCR, the in vitro secretion of pro- and anti-inflammatory cytokines and their capacity to induce pro-inflammatory T cells.ResultsObesity, similar to aging, induced increased serum levels of pro-inflammatory cytokines and autoimmune antibodies, while vaccine-specific antibodies were reduced. In agreement with the serum results, the B cell pool of obese adults and elderly individuals was enriched in pro-inflammatory B cell subsets and was characterized by higher expression of markers associated with cell senescence, higher levels of T-bet, the transcription factor for autoimmune antibodies and lower levels of E47, the transcription factor associated with protective responses to the influenza vaccine. B cells from obese adults and elderly individuals were also able to secrete inflammatory cytokines and support the generation of inflammatory T cells. All these pro-inflammatory characteristics of B cells from obese individuals were significantly attenuated, but not completely reversed, by weight loss.ConclusionsAlthough the results from our small observational study show that obesity-induced dysfunctional B cell responses, similar to those occurring during aging, are ameliorated in some but not all obese individuals after weight loss, the effects of body weight loss on mechanistic pathways are largely missing and deserve further investigation.

Improved serologic responses to DTaP over Tdap vaccination in adult hematopoietic cell transplant recipients.

Hematopoietic cell transplantation (HCT) recipients have reduced antibody titers to tetanus, diphtheria, and pertussis. Tdap is approved for revaccinating adult HCT recipients in the United States, whereas DTaP is not approved in this population. To our knowledge, no studies to date have compared responses to DTaP versus Tdap in adult HCT patients. We conducted a retrospective study comparing responses to DTaP versus Tdap vaccines in otherwise similar adult HCT patients in order to determine if one of these vaccines elicits superior antibody responses. We evaluated 43 allogeneic and autologous transplant recipients as a combined cohort and as separate subsets for vaccine specific antibody titers and proportion of strong vaccine responders. Subset analysis focused on the autologous transplant recipients. Higher median antibody titers were found to all vaccine components among DTaP recipients (diphtheria p = .021, pertussis p = .020, tetanus p = .007). DTaP recipients also had more strong responders to diphtheria and pertussis (diphtheria p = .002, pertussis p = .006). Among the autologous HCT recipient subset, there were more strong responders to diphtheria (p = .036). Our data shows that post-HCT vaccination with DTaP leads to higher antibody titers and more strong responders, which suggests that DTaP is more effective than Tdap in HCT recipients.

Potentiating the Cross-Reactive IFN-γ T Cell and Polyfunctional T Cell Responses by Heterologous GX-19N DNA Booster in Mice Primed with Either a COVID-19 mRNA Vaccine or Inactivated Vaccine.

Waning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potential of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or an mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T Cells to the SARS-CoV-2 variant of concern (VOC), compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T Cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, the heterologous GX-19N boost induced higher S-specific polyfunctional CD4+ and CD8+ T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants.

NEI supplementation improves alum-based immunity in CFTR KO mice

Abstract Cystic fibrosis (CF) is a genetic disorder that causes severe damage to the lungs and digestive system. CF affects the cells that produce mucus, sweat, and digestive enzymes and is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Expression and function of CFTR have been extensively studied on epithelial cells and several recent publications have shown that CFTR also regulates the functions of myeloid cells. We addressed whether CFTR is expressed by B cells and the role of CFTR in B cell functions. We found that CFTR is expressed on murine and human B cells. Compared to control wild-type (WT) mice, CFTR KO exhibited reduced frequency of B cells in lymphoid tissues and lower levels of serum immunoglobulin isotypes. Upon systemic immunization with an alum-based vaccine, CFTR KO mice developed lower antibody responses than control mice. Interestingly, vaccine supplementation with an inhibitor of the serine protease elastase (NEI) enhanced the titers of vaccine-specific serum antibody responses in CFTR KO mice and CFTR heterozygote (CFTR Het) mice. We have previously reported that NEI supplementation could promote mucosal immunity in mice immunized with the alum-based injected vaccine. In this regard, CFTR KO and CFTR Het mice immunized with NEI-supplemented alum-based injected developed higher IgA and IgG responses in saliva than control WT mice. These results provide new insights on the regulatory role of CFTR for B cell differentiation and function. They also suggest that vaccine supplementation with NEI could improve protection of individuals leaving with CF against respiratory pathogens. NIH R01 DK101323

The Pregnancy, Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh.

Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity. The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy. The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018-2019. Prospective, longitudinal pregnancy and birth cohort. We conducted home visits to enrol pregnant women in the late first or early second trimester (11-17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants. We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 μg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1)μg/L and 33.1 (19.6, 56.5)μg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴=0.72) among women with water arsenic ≥ median but weakly correlated (⍴=0.17) among women with water arsenic < median. The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. NCT03930017.