Differences In Antibody Responses Research Articles

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort.

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.

A heptavalent O-antigen bioconjugate vaccine exhibits differential functional antibody responses against diverse Klebsiella pneumoniae isolates.

Klebsiella pneumoniae is the leading cause of neonatal sepsis and is increasingly difficult to treat due to antibiotic resistance. Vaccination represents a tractable approach to combat this resistant bacterium; however, there is currently not a licensed vaccine. Surface polysaccharides, including O-antigens of lipopolysaccharide, have long been attractive candidates for vaccine inclusion. Herein we describe the generation of a bioconjugate vaccine targeting seven predominant O-antigen subtypes in K. pneumoniae. Each bioconjugate was immunogenic in isolation, with limited cross-reactivity among subtypes. Vaccine-induced antibodies demonstrated varying degrees of binding to a wide variety of K. pneumoniae strains. Further, sera from vaccinated mice induced complement-mediated killing of many of these strains. Finally, increased capsule interfered with O-antigen antibodies' ability to bind and mediate killing of some K. pneumoniae strains. Taken together, these data indicate that this novel heptavalent O-antigen bioconjugate vaccine formulation exhibits limited efficacy against some, but not all, K. pneumoniae isolates.

Differences in the microbiome of the small intestine of Leghorn lines divergently selected for antibody titer to sheep erythrocytes suggest roles for commensals in host humoral response.

For forty generations, two lines of White Leghorn chickens have been selected for high (HAS) or low (LAS) antibody response to a low dose injection of sheep red blood cells (SRBCs). Their gut is home to billons of microorganisms and the largest number of immune cells in the body; therefore, the objective of this experiment was to gain understanding of the ways the microbiome may influence the differential antibody response observed in these lines. We achieved this by characterizing the small intestinal microbiome of HAS and LAS chickens, determining their functional microbiome profiles, and by using machine learning to identify microbes which best differentiate HAS from LAS and associating the abundance of those microbes with host gene expression. Microbiome sequencing revealed greater diversity in LAS but statistically higher abundance of several strains, particularly those of Lactobacillus, in HAS. Enrichment of microbial metabolites implicated in immune response such as lactic acid, short chain fatty acids, amino acids, and vitamins were different between HAS and LAS. The abundance of several microbial strains corresponds to enriched host gene expression pathways related to immune response. These data provide a compelling argument that the microbiome is both likely affected by host divergent genetic selection and that it exerts influence on host antibody response by various mechanisms.

Cytokine signature in convalescent SARS-CoV-2 patients with inflammatory bowel disease receiving vedolizumab

While differential antibody responses SARS-CoV-2 in patients with inflammatory bowel disease (IBD) receiving infliximab and vedolizumab are well-characterized, the immune pathways underlying these differences remain unknown. Prior to COVID-19 vaccine development, we screened 235 patients with IBD receiving biological therapy for antibodies to SARS-CoV-2 and measured serum cytokines. In seropositive patients, we prospectively collected clinical data. We found a cytokine signature in patients receiving vedolizumab who are seropositive compared with seronegative for SARS-CoV-2 antibodies that may be linked to repeated SARS-CoV-2 infections. However, there were no differences between seropositive and seronegative patients receiving infliximab. In this single-center cohort of patients with IBD with anti-SARS-CoV-2 antibodies at the onset of the COVID-19 pandemic, and therefore without influence of vaccination, there is a cytokine signature in patients receiving vedolizumab but not infliximab. These findings lay the groundwork for further studies on immune consequences of viral infection in patients with IBD, which is postulated to evolve from aberrant host-microbe responses.

SARS-CoV-2 mRNA vaccination induces an intranasal mucosal response characterized by neutralizing antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced systemic antibody profiles are well characterized; however, little is known about whether intranasal mucosal antibodies are induced or can neutralize virus in response to mRNA vaccination. We sought to evaluate intranasal mucosal antibody production with SARS-CoV-2 mRNA vaccination. SARS-CoV-2-specific IgG and IgA concentrations and neutralization activity from sera and nasal mucosa via nasal epithelial lining fluid (NELF) collection were measured in SARS-CoV-2 mRNA-vaccinated healthy volunteers (N= 29) by using multiplex immunoassays. Data were compared before and after vaccination, between mRNA vaccine brands, and by sex. SARS-CoV-2 mRNA vaccination induced an intranasal immune response characterized by neutralizing mucosal antibodies. IgG antibodies displayed greater Spike 1 (S1) binding specificity than did IgA in serum and nasal mucosa. Nasal antibodies displayed greater neutralization activity against the receptor-binding domain than serum. Spikevax (Moderna)-vaccinated individuals displayed greater SARS-CoV-2-specific IgG and IgA antibody concentrations than did Comirnaty (BioNTech/Pfizer)-vaccinated individuals in their serum and nasal epithelial lining fluid. Sex-dependent differences in antibody response were not observed. SARS-CoV-2 mRNA vaccination induces a robust systemic and intranasal antibody production with neutralizing capacity. Spikevax vaccinations elicit a greater antibody response than does Comirnaty vaccination systemically and intranasally.

Serological analysis reveals differential antibody responses between TB patients and latently infected individuals from the TB endemic country of Mozambique.

Serological antibody profiling of tuberculosis (TB) patients and household contacts with latent TB infection (LTBI) could identify risk indicators of disease progression, and potentially also serve as an easily accessible diagnostic tool to discriminate between these two stages of Mycobacterium tuberculosis (Mtb) infection. Yet, despite significant efforts over many decades, neither application has yet fully materialised, and this is at least in part due to inconsistent and varying antibody profiles from different TB endemic regions. In this study, we conducted a retrospective exploratory analysis of serum antibodies in a cohort of active TB patients (ATB) and their interferon-gamma release assay (IGRA) positive household contacts (LTBI), as well as healthy controls (HC) from Mozambique, a country with a high TB burden from the Sub-Saharan region. Using several Mtb antigens as well as crude preparations of culture filtrate proteins (CFP) from Mtb and Bacille Calmette Guérin (BCG), we report that the most discriminatory response for TB and LTBI was observed for serum IgA antibodies to the MPT64 antigen, followed by IgG antibodies to Ag85B and CFP, with ATB patients having significantly higher levels than LTBI or BCG-vaccinated healthy controls. Conversely, sera from LTBI individuals had higher levels of IgG antibodies to the HBHA antigen than ATB. While our sample size (n = 21 for ATB, 18 for LTBI and 17 for HC) was too small to fully evaluate the diagnostic potential of these differing serological profiles, our study however preliminarily indicated high level of sensitivity (95%) and specificity (97%) of an ELISA MPT64-IgA test for discriminating TB from LTBI and healthy controls, supporting the notion that it alone, or possibly in combination with other antigens such as Ag85B or CFP could lead to development of an easily accessible diagnostic tool for TB.

Exploring the Effects of Vitamin D and Vitamin A Levels on the Response to COVID-19 Vaccine.

COVID-19 vaccines were developed at an unprecedented speed in history. The factors affecting the response to COVID-19 vaccines are not clear. Herein, the effects of vitamin D and vitamin A (retinol) levels on the response to the BNT162b2 vaccine were explored. A total of 124 vaccine recipients were recruited from the general population attending vaccination centers in Irbid, Jordan. Blood samples were collected immediately before receiving the first vaccine dose (D0) and three weeks later (D21). Baseline (D0) levels of 25-hydroxyvitamin D [25(OH)D], retinol, and SARS-CoV-2 S1 IgG antibodies were measured with ELISA. The response to the BNT162b2 vaccine was tested by measuring the levels and avidity of SARS-CoV-2 S1 IgG antibodies on D21. The participants were divided into two groups, unexposed and exposed, based on the D0 SARS-CoV-2 antibody results. No significant correlation was found between the levels of 25(OH)D or retinol and the levels, avidity, or fold increase of antibodies in both groups. Similarly, no significant difference in antibody response was found between 25(OH)D status groups, retinol status groups, or combined status groups. These findings show that the baseline vitamin D or vitamin A levels have no effect on the short-term response to a single dose of BNT162b2 vaccine.

Efficacy of COVID-19 vaccines in inflammatory bowel disease patients receiving anti-TNF therapy: A systematic review and meta-analysis

Background and objectivesThere are concerns about the serological responses to Coronavirus disease 2019 (COVID-19) vaccines in inflammatory bowel disease (IBD) patients, particularly those receiving anti-TNF therapy. This study aimed to systematically evaluate the efficacy of COVID-19 vaccines in IBD patients receiving anti-TNF therapy. MethodsElectronic databases were searched to identify relevant studies. We calculated pooled seroconversion rate after COVID-19 vaccination and subgroup analysis for vaccine types and different treatments were performed. Additionally, we estimated pooled rate of T cell response, neutralization response, and breakthrough infections in this population. Results32 studies were included in the meta-analysis. IBD patients receiving anti-TNF therapy had relatively high overall seroconversion rate after complete vaccination, with no statistical difference in antibody responses associated with different drug treatments. The pooled positivity rate of T cell response was 0.85 in IBD patients receiving anti-TNF therapy. Compared with healthy controls, the positivity of neutralization assays was significantly lower in IBD patients receiving anti-TNF therapy. The pooled rate of breakthrough infections in IBD patients receiving anti-TNF therapy was 0.04. ConclusionsCOVID-19 vaccines have shown good efficacy in IBD patients receiving anti-TNF therapy. However, IBD patients receiving anti-TNF have a relatively high rate of breakthrough infections and a low level of neutralization response.

Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity

Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection. It has been proposed that Long Covid is a consequence of either an excessive or inadequate initial immune response. Here, we analyze SARS-CoV-2 humoral and cellular immunity in 86 healthcare workers with laboratory confirmed mild or asymptomatic SARS-CoV-2 infection during the first wave. Symptom questionnaires allow stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observe no difference in antibody responses to spike RBD or nucleoprotein, virus neutralization, or T cell responses. Also, there is no difference in the profile of antibody waning. Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again shows similar SARS-CoV-2 immunity. Thus, quantitative differences in these measured parameters of SARS-CoV-2 adaptive immunity following mild or asymptomatic acute infection are unlikely to have contributed to Long Covid causality. ClinicalTrials.gov (NCT04318314).

Novel bioinformatic methods and machine learning approaches reveal candidate biomarkers of the intensity and timing of past exposure to Plasmodium falciparum.

Accurately quantifying the burden of malaria over time is an important goal of malaria surveillance efforts and can enable effective targeting and evaluation of interventions. Malaria surveillance methods capture active or recent infections which poses several challenges to achieving malaria surveillance goals. In high transmission settings, asymptomatic infections are common and therefore accurate measurement of malaria burden demands active surveillance; in low transmission regions where infections are rare accurate surveillance requires sampling large subsets of the population; and in any context monitoring malaria burden over time necessitates serial sampling. Antibody responses to Plasmodium falciparum parasites persist after infection and therefore measuring antibodies has the potential to overcome several of the current obstacles to accurate malaria surveillance. Identifying which antibody responses are markers of the timing and intensity of past exposure to P. falciparum remains challenging, particularly among adults who tend to be re-exposed multiple times over the course of their lifetime and therefore have similarly high antibody responses to many Plasmodium antigens. A previous analysis of 479 serum samples from individuals in three regions in southern Africa with different historical levels of P. falciparum malaria transmission (high, intermediate, and low) revealed regional differences in antibody responses to P. falciparum antigens among children under 5 years of age. Using a novel bioinformatic pipeline optimized for protein microarrays that minimizes between-sample technical variation, we used antibody responses to Plasmodium antigens as predictors in random forest models to classify samples from adults into these three regions of differing historical malaria transmission with high accuracy (AUC = 0.99). Many of the most important antigens for classification in these models do not overlap with previously published results and are therefore novel candidate markers for the timing and intensity of past exposure to P. falciparum. Measuring antibody responses to these antigens could lead to improved malaria surveillance.

Two Novel Adenovirus Vectors Mediated Differential Antibody Responses via Interferon-α and Natural Killer Cells.

Recombinant adenovirus vectors have been widely used in vaccine development. To overcome the preexisting immunity of human adenovirus type 5 (Ad5) in populations, a range of chimpanzee or rare human adenovirus vectors have been generated. However, these novel adenovirus vectors mediate the diverse immune responses in the hosts. In this study, we explored the immune mechanism of differential antibody responses to SARS-CoV-2 S protein in mice immunized by our previously developed two novel simian adenovirus type 23 (Sad23L) and human adenovirus type 49 (Ad49L), and Ad5 vectored COVID-19 vaccines. Sad23L-nCoV-S and Ad5-nCoV-S vaccines induced the low level of interferon-α (IFN-α) and the high level of antigen-specific antibody responses in wild-type and IFN-α/β receptor defective (IFNAR-/-) C57 mice, while Ad49L-nCoV-S vaccine induced the high IFN-α and low antibody responses in C57 mice but the high antibody response in IFNAR-/- mice. In addition, the high antibody response was detected in natural killer (NK) cells-blocked but the low in follicular helper T (TFH) cells -blocked C57 mice immunized with Ad49L-nCoV-S vaccine. These results showed that Ad49L vectored vaccine stimulated IFN-α secretion to activate NK cells, and then reduced the number of TFH cells, generation center (GC) B cells and plasma cells, and subsequently reduced antigen-specific antibody production. The different novel adenovirus vectors could be selected for vaccine development according to the need for either humoral or cellular or both immune protections against a particular disease. IMPORTANCE Novel adenovirus vectors are an important antigen delivery platform for vaccine development. Understanding the immune diversity between different adenoviral vectors is critical to design the proper vaccine against an aim disease. In this study, we described the immune mechanism of Sad23L and Ad49L vectored vaccines for raising the equally high specific T cell response but the different level of specific antibody responses in mice. We found that Ad49L-vectored vaccine initiated the high IFN-α and activated NK cells to inhibit antibody response via downregulating the number of CD4+ TFH cells leading to the decline of GC B cells and plasma cells.

Seroprevalence and durability of antibody responses to AstraZeneca vaccination in Ugandans with prior mild or asymptomatic COVID-19: implications for vaccine policy.

The duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan Africa are crucial for guiding pandemic policy interventions, but systematic data for this region is scarce. This study investigated the antibody response after AstraZeneca vaccination in COVID-19 convalescent Ugandans. We recruited 86 participants with a previous rt-PCR-confirmed mild or asymptomatic COVID-19 infection and measured the prevalence and levels of spike-directed IgG, IgM, and IgA antibodies at baseline, 14 and 28 days after the first dose (priming), 14 days after the second dose (boosting), and at six- and nine-months post-priming. We also measured the prevalence and levels of nucleoprotein-directed antibodies to assess breakthrough infections. Within two weeks of priming, vaccination substantially increased the prevalence and concentrations of spike-directed antibodies (p < 0.0001, Wilcoxon signed rank test), with 97.0% and 66% of vaccinated individuals possessing S-IgG and S-IgA antibodies before administering the booster dose. S-IgM prevalence changed marginally after the initial vaccination and barely after the booster, consistent with an already primed immune system. However, we also observed a rise in nucleoprotein seroprevalence, indicative of breakthroughs six months after the initial vaccination. Our results suggest that vaccination of COVID-19 convalescent individuals with the AstraZeneca vaccine induces a robust and differential spike-directed antibody response. The data highlights the value of vaccination as an effective method for inducing immunity in previously infected individuals and the importance of administering two doses to maintain protective immunity. Monitoring anti-spike IgG and IgA when assessing vaccine-induced antibody responses is suggested for this population; assessing S-IgM will underestimate the response. The AstraZeneca vaccine is a valuable tool in the fight against COVID-19. Further research is needed to determine the durability of vaccine-induced immunity and the potential need for booster doses.

Differential T-cell and antibody responses induced by mRNA versus adenoviral vectored COVID-19 vaccines in patients with immunodeficiencies.

Immunodeficient patients (IDPs) are at higher risk of contracting severe coronavirus disease 2019 (COVID-19). Targeted vaccination strategies have been implemented to enhance vaccine-induced protection. In this population, however, clinical effectiveness is variable and the duration of protection unknown. We sought to better understand the cellular and humoral immune responses to mRNA and adenoviral vectored COVID-19 vaccines in patients with immunodeficiency. Immune responses to severe acute respiratory syndrome coronavirus 2 spike were assessed after 2 doses of homologous ChAdOx1-nCoV-19 or BNT162b2 vaccines in 112 infection-naive IDPs and 131 healthy health care workers as controls. Predictors of vaccine responsiveness were investigated. Immune responses to vaccination were low, and virus neutralization by antibody was not detected despite high titer binding responses in many IDPs. In those exhibiting response, the frequency of specific T-cell responses in IDPs was similar to controls, while antibody responses were lower. Sustained vaccine specific differences were identified: T-cell responses were greater in ChAdOx1-nCoV-19- compared to BNT162b2-immunized IDPs, and antibody binding and neutralization were greater in all cohorts immunized with BNT162b2. The positive correlation between T-cell and antibody responses was weak and increased with subsequent vaccination. Immunodeficient patients have impaired immune responses to mRNA and viral vector COVID-19 vaccines that appear to be influenced by vaccine formulation. Understanding the relative roles of T-cell- and antibody-mediated protection as well as the potential of heterologous prime and boost immunization protocols is needed to optimize the vaccination approach in these high-risk groups.

Differential dengue antibody responses in recipients of a Zika DNA vaccine are governed by dengue immune history

Abstract Dengue virus (DENV 1–4) and Zika virus (ZIKV) are closely related flaviviruses that induce immunological cross-reactivity. The VRC5283 Zika virus wild type DNA vaccine is the first to complete a Phase 2b trial (NCT03110770). The objective of this study was to test if VRC5283 induced potent ZIKV-specific neutralizing antibodies (NAbs) while avoiding priming of cross-reactive antibodies that could potentially enhance dengue disease. Here, we measured NAbs to DENV1–4 and ZIKV in serum samples obtained from individuals living in dengue-endemic (Puerto Rico) and non-endemic areas (Texas) immunized with VRC5283 at weeks 0, 4, and 8. We performed plaque reduction neutralization tests (PRNT 50) with sera collected at weeks 0 and 16 after final vaccination. Sera were tested for ZIKV isolated in Brazil, and DENV1–4 isolated in Sri Lanka. Most individuals from dengue-endemic areas had NAbs &amp;gt;1:20 to DENV1–4 and ZIKV prior to vaccination, with the highest NAb titers to DENV2. VRC5283 boosted immunity across all flaviviruses in the dengue-endemic cohort, with an 8.47-fold increase in ZIKV, 2.76-fold increase in DENV1, 1.67-fold increase in DENV3 and 2.06-fold increase in DENV4 titers, but did not significantly boost DENV2 titers. Sera from non-endemic areas had no NAbs to DENV1–4 or ZIKV prior to vaccination, and a boost in NAbs following vaccination was observed only to ZIKV. Thus, VRC5283 only induces dengue cross-reactive NAbs in individuals with prior dengue immunity. Ongoing testing with binding assays will further evaluate whether vaccination induced beneficial or enhancing antibodies to DENV1–4. This work was supported by the Intramural Research Program of NIAID.

Seroconversion following a booster dose of COVID-19 vaccine in liver transplant recipients: a systematic review and meta-analysis.

Although it is well established that 2 doses of COVID‑19 vaccines are associated with reduced immune responses in liver transplant recipients (LTRs), studies regarding their immunogenicity and tolerability after a booster dose are limited. We aimed to review the available literature data regarding antibody responses and safety of the third dose of COVID‑19 vaccines in LTRs. We searched PubMed and Google Scholar for eligible studies. The primary outcome was to compare the rates of seroconversion after the second and third dose of COVID‑19 vaccine in LTRs. This meta‑analysis was performed using a generalized linear mixed model and the Clopper and Pearson method was employed to calculate the 2‑sided CIs. Six prospective studies involving 596 LTRs met the inclusion criteria. The pooled rate of antibody response before the third dose was 71% (95% CI, 56%-83%; heterogeneity, I2 = 90%; P <0.001), while after the third dose it was 94% (95% CI, 91%-96%; heterogeneity, I2 = 17%; P = 0.31). There was no difference in antibody responses after the third dose in relation to the use of calcineurin inhibitors (P = 0.44) or mammalian target of rapamycin inhibitors (P = 0.33), while the pooled rate of antibody responses in the patients on mycophenolate mofetil (MMF) was 88% (95% CI, 83%-92%; heterogeneity, I2 = 0%; P = 0.57). It was significantly lower (P <0.001), as compared with those on MMF‑free immunosuppression (pooled rate, 97%; 95% CI, 95%-98%; heterogeneity, I2 = 30%; P = 0.22). No safety concerns were reported for the booster dose. Our meta‑analysis demonstrated that the third dose of COVID‑19 vaccines induced adequate humoral and cellular immune responses in LTRs, while MMF remained a negative predictor of immunologic responses.

Sağlık Çalışanlarında COVID-19‘a Karşı İnaktif ve mRNA Aşılanma Sonrası Doz Sayısına Bağlı Antikor Yanıtı ve Yan Etkilerin Değerlendirilmesi

Introduction: Studies are showing that a high antibody response increases the protection against variants in the fight against the COVID-19 pandemic. In this study, we aimed to investigate the relationship between antibody response and side effects based on the number of doses administered to healthcare workers who were vaccinated against COVID-19. Materials and Methods: Healthcare workers, who were vaccinated with two doses of BNT162b2 (Group 1), a single dose of BNT162b2 following two doses of CoronaVac (Group 2), or two doses of BNT162b2 following two doses of CoronaVac (Group 3), were randomly assigned to this study. Serum samples were taken from the participants 30 ± 2 days after the last vaccination date, and the SARSCoV-2 anti-spike S1 RBD IgG test was administered to these samples. A questionnaire was conducted detailing the demographics of the patients as well as their post-vaccination complaints. The results were analyzed statistically. Analysis results with a p-value of &lt;0.05 were considered significant. Results: A total of 179 healthcare professionals with a mean age of 41.7 ± 10.6 years were included in our study. Of the studied samples, 95.5% (n= 171) were interpreted as anti-spike S1 RBD IgG seropositive. Positivity rates and mean antibody levels were 93.2%, 95.9%, 97.8%, and 107.4 ± 117.1, 152.7 ± 108.5, 201.4 ± 114.9 (AU/mL) for Group 1, Group 2, and Group 3, respectively (p&lt; 0.05). In general, no significant differences in antibody response were seen based on gender or age. However, a significant correlation was found between the occurrence of vaccine-related side effects and antibody titer (p&lt; 0.001). The most common side effect was pain in the area where the vaccine was administered, with a rate of 77.4% (n= 48). More vaccine-related side effects were reported in participants under the age of 40 and in female healthcare workers. Conclusion: We believe that booster doses are effective for increasing the immune response and thus protecting against COVID-19. More extensive research should be conducted to confirm the link between the occurrence of vaccine-related side effects and antibody titer. Furthermore, studies on the safety of increasing the number of vaccine doses are required.

Immune profiling of SARS-CoV-2 epitopes in asymptomatic and symptomatic pediatric and adult patients

BackgroundThe infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unpredictable manifestations of coronavirus disease (COVID-19) and variable clinical course with some patients being asymptomatic whereas others experiencing severe respiratory distress, or even death. We aimed to evaluate the immunoglobulin G (IgG) response towards linear peptides on a peptide array containing sequences from SARS-CoV-2, Middle East respiratory syndrome-related coronavirus (MERS) and common-cold coronaviruses 229E, OC43, NL63 and HKU1 antigens, in order to identify immunological indicators of disease outcome in SARS-CoV-2 infected patients.MethodsWe included in the study 79 subjects, comprising 19 pediatric and 30 adult SARS-CoV-2 infected patients with increasing disease severity, from mild to critical illness, and 30 uninfected subjects who were vaccinated with one dose of SARS-CoV-2 spike mRNA BNT162b2 vaccine. Serum samples were analyzed by a peptide microarray containing 5828 overlapping 15-mer synthetic peptides corresponding to the full SARS-CoV-2 proteome and selected linear epitopes of spike (S), envelope (E) and membrane (M) glycoproteins as well as nucleoprotein (N) of MERS, SARS and coronaviruses 229E, OC43, NL63 and HKU1 (isolates 1, 2 and 5).ResultsAll patients exhibited high IgG reactivity against the central region and C-terminus peptides of both SARS-CoV-2 N and S proteins. Setting the threshold value for serum reactivity above 25,000 units, 100% and 81% of patients with severe disease, 36% and 29% of subjects with mild symptoms, and 8% and 17% of children younger than 8-years reacted against N and S proteins, respectively. Overall, the total number of peptides in the SARS-CoV-2 proteome targeted by serum samples was much higher in children compared to adults. Notably, we revealed a differential antibody response to SARS-CoV-2 peptides of M protein between adults, mainly reacting against the C-terminus epitopes, and children, who were highly responsive to the N-terminus of M protein. In addition, IgG signals against NS7B, NS8 and ORF10 peptides were found elevated mainly among adults with mild (63%) symptoms. Antibodies towards S and N proteins of other coronaviruses (MERS, 229E, OC43, NL63 and HKU1) were detected in all groups without a significant correlation with SARS-CoV-2 antibody levels.ConclusionsOverall, our results showed that antibodies elicited by specific linear epitopes of SARS-CoV-2 proteome are age dependent and related to COVID-19 clinical severity. Cross-reaction of antibodies to epitopes of other human coronaviruses was evident in all patients with distinct profiles between children and adult patients. Several SARS-CoV-2 peptides identified in this study are of particular interest for the development of vaccines and diagnostic tests to predict the clinical outcome of SARS-CoV-2 infection.

Linking the outer membrane composition of salmonella to protective antibody responses.

Invasive non-typhoidal Salmonella (iNTS) infection has a high risk of fatality. Currently, there is no licensed vaccine against iNTS, making creating an effective vaccine priority for regions where the rate of these infections is high. In particular, an ideal vaccine should be protective against multiple serovars of Salmonella. The correlation of the protective properties of antibodies raised against Salmonella with distinct types and lengths of O-antigen repeats and membrane proteins has not been thoroughly investigated yet, but experiments conducted on mice have revealed some important differences. We hypothesize that these differences can be explained by the physical structure of the bacterial outer envelope and the accessibility of proteinaceous epitopes to antibodies. To test this hypothesis, we modeled the outer membrane for two of the most common iNTS serovars, Salmonella enterica Enteritidis (SEn) and Typhimurium (STm), along with the outer membrane proteins OmpD and OmpA. We set up all-atomic molecular simulations (MD) for both proteins separately for the serotypes STm and SEn, and for LPS with different lengths of O4 and O9 O-Ag repeats, giving, overall, 20 systems for 1.5 microseconds each. From these MD simulations, we measured various quantities, including Solvent Accessible Surface Area (SASA) of extracellular loops of the proteins, root-mean-square fluctuation (RMSF) of the residues, and the protein to O-Ag contact area, in order to explain the molecular underpinnings of differential antibody responses being raised by distinct serotypes.

Adjuvant-Mediated Differences in Antibody Responses to Computationally Optimized Hemagglutinin and Neuraminidase Vaccines.

Computationally optimized broadly reactive antigens (COBRAs) are a next-generation universal influenza vaccine candidate. However, how these COBRAs induce antibody responses when combined with different adjuvants has not previously been well-characterized. Therefore, we performed in vivo studies with an HA-based H1 COBRA, Y2, and an NA-based N1 COBRA, N1-I, to assess this effect for the H1N1 subtype. We tested the adjuvants AddaVax, AddaS03, CpG, and Alhydrogel. AddaS03 performed the best, eliciting high IgG titers and hemagglutination inhibition (HAI) activity for Y2 immunizations. Interestingly, serum antibody epitopes were relatively similar across adjuvant groups. Moreover, following N1-I immunization with these adjuvants, AddaS03 also elicited the highest IgG and neuraminidase inhibition (NAI) titers against the 2009 pandemic virus, A/California/07/2009 (A/CA/09). These results inform adjuvant selection efforts for H1 and N1 COBRA HA and NA antigens in a mouse model.

Reduced antibody response to SARS-CoV-2 in COVID-19 patients with newly diagnosed diabetes: a retrospective observational study

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has dramatically impacted global health, and patients with type 2 diabetes have been identified as a high-risk group for COVID-19 infection and the development of severe disease. In response, this study aimed to evaluate whether patients with type 2 diabetes infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could develop antibody responses in the same manner as patients without diabetes, and whether there is a difference in antibody response to SARS-CoV-2 between patients with diabetes diagnosed prior to hospitalization, and those with newly diagnosed diabetes.MethodsSARS-CoV-2-specific immunoglobulin G (IgG) levels were quantified using two iFlash 3000 Chemiluminescence Immunoassay analyzer kits (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for nucleocapsid protein (IgG-N), and specific for the S1 subunit of the spike protein (IgG-S1). In 124 hospitalized patients with COVID-19, 40 patients with type 2 diabetes were matched to 40 patients without diabetes using propensity score matching (PSM).ResultsThere was no difference in IgG-N and IgG-S1 levels between the patients with diabetes and those without. Of patients with diabetes, 31 patients had known diabetes and nine patients had newly diagnosed diabetes. The median levels of IgG-N at 7–13 days in patients with newly diagnosed diabetes were significantly lower than those in patients with known diabetes (IgG-N; 10.9 vs. 31.0 AU/mL, p = 0.031, IgG-S1; 7.5 vs. 24.4 AU/mL, p = 0.023).ConclusionsEven after adjusting for covariates using PSM, COVID-19 patients with type 2 diabetes had comparable antibody responses to patients without diabetes. Patients with newly diagnosed diabetes had lower IgG-N and IgG-S1 production in the second week of the disease compared with those with previously known diabetes.