IgA Antibodies Research Articles

The dynamics and determinants of specific systemic and mucosal antibody responses to SARS-CoV-2 in three adult cohorts in the Ecuadorian Andes: a study protocol.

There are limited longitudinal data on the systemic and mucosal antibody responses to SARS-CoV-2 from Latin America, a region severely affected by COVID-19, and where vaccine strategies have been implemented during the evolving pandemic. To evaluate determinants of seroprevalence and changes in levels of anti-SARS-CoV-2 antibodies longitudinally in adults with different levels of exposure to SARS-CoV-2 (defined a priori as low, medium, and high based on presumed occupational risk), in two Andean cities in Ecuador. Longitudinal cohort study of 1,000 adults aged 18 years and older with questionnaire data and sample collection done at 0, 3, 6, and 12 months during the period 2020-2023. Observations collected included WHO-ISARIC questionnaire and peripheral blood and saliva samples for measurement of IgG and IgA antibodies, respectively. Planned analyses are tailored to the longitudinal nature of the outcomes defined by participants' antibody levels and aim at estimating their average trends with time since infection in each of the occupational groups, adjusted for demographics and calendar-time levels of SARS-CoV-2 infection in the general population. The latter reflect the impact of the national control measures such as vaccinations and movement restrictions. Understanding the duration and the dynamics of waning immunity to SARS-CoV-2, in the context of exposures to emerging virus variants and immunization, will inform the implementation of targeted public health strategies in the Latin American region. This study will observe the bioethical principles of the Declaration of Helsinki. Informed written consent will be obtained. Samples from participants will be stored for up to three years after which they will be destroyed. The study protocol was approved by the Ecuadorian Ministry of Public Health Ethics Committee for COVID-19 Research. Antibody results will be provided to participants and participating institutions and to the national health authorities.

Cholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants.

Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children.

Maternal-Foetal/Infant Interactions-Gut Microbiota and Immune Health.

In recent years, the number of scientific publications on the role of intestinal microbiota in shaping human health, as well as the occurrence of intestinal dysbiosis in various disease entities, has increased dynamically. However, there is a gap in comprehensively understanding the factors influencing a child's gut microbiota. This review discusses the establishment of gut microbiota and the immunological mechanisms regulating children's microbiota, emphasising the importance of prioritising the development of appropriate gut microbiota in a child from the planning stages of pregnancy. The databases PubMed, Web of Sciences, Cochrane, Scopus and Google Scholar were searched to identify relevant articles. A child's gut microbiota composition is influenced by numerous factors, such as diet during pregnancy, antibiotic therapy, the mother's vaginal microbiota, delivery method, and, later, feeding method and environmental factors. During pregnancy, the foetus naturally acquires bacterial strains from the mother through the placenta, thereby shaping the newborn's immune system. Inappropriate maternal vaginal microbiota may increase the risk of preterm birth. Formula-fed infants typically exhibit a more diverse microbiota than their breastfed counterparts. These factors, among others, shape the maturation of the child's immune system, impacting the production of IgA antibodies that are central to cellular humoral immune defence. Further research should focus on identifying specific microbiota-immune system interactions influencing a child's immune health and developing personalised treatment strategies for immune-related disorders.

Humoral immunoprofiling identifies novel biomarkers and an immune suppressive autoantibody phenotype at the site of disease in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer, with minimal response to therapeutic intervention and with 85% of cases diagnosed at an advanced stage due to lack of early symptoms, highlighting the importance of understanding PDAC immunology in greater detail. Here, we applied an immunoproteomic approach to investigate autoantibody responses against cancer-testis and tumor-associated antigens in PDAC using a high-throughput multiplexed protein microarray platform, comparing humoral immune responses in serum and at the site of disease in order to shed new light on immune responses in the tumor microenvironment. We simultaneously quantified serum or tissue IgG and IgA antibody isotypes and subclasses in a cohort of PDAC, disease control and healthy patients, observing inter alia that subclass utilization in tumor tissue samples was predominantly immune suppressive IgG4 and inflammatory IgA2, contrasting with predominant IgG3 and IgA1 subclass utilization in matched sera and implying local autoantibody production at the site of disease in an immune-tolerant environment. By comparison, serum autoantibody subclass profiling for the disease controls identified IgG4, IgG1, and IgA1 as the abundant subclasses. Combinatorial analysis of serum autoantibody responses identified panels of candidate biomarkers. The top IgG panel included ACVR2B, GAGE1, LEMD1, MAGEB1 and PAGE1 (sensitivity, specificity and AUC values of 0.933, 0.767 and 0.906). Conversely, the top IgA panel included AURKA, GAGE1, MAGEA10, PLEKHA5 and XAGE3aV1 (sensitivity, specificity, and AUC values of 1.000, 0.800, and 0.954). Assessment of antigen-specific serum autoantibody glycoforms revealed abundant sialylation on IgA in PDAC, consistent with an immune suppressive IgA response to disease.

Immunoinformatic Identification of Multiple Epitopes of gp120 Protein of HIV-1 to Enhance the Immune Response against HIV-1 Infection.

Acquired Immunodeficiency Syndrome is caused by the Human Immunodeficiency Virus (HIV), and a significant number of fatalities occur annually. There is a dire need to develop an effective vaccine against HIV-1. Understanding the structural proteins of viruses helps in designing a vaccine based on immunogenic peptides. In the current experiment, we identified gp120 epitopes using bioinformatic epitope prediction tools, molecular docking, and MD simulations. The Gb-1 peptide was considered an adjuvant. Consecutive sequences of GTG, GSG, GGTGG, and GGGGS linkers were used to bind the B cell, Cytotoxic T Lymphocytes (CTL), and Helper T Lymphocytes (HTL) epitopes. The final vaccine construct consisted of 315 amino acids and is expected to be a recombinant protein of approximately 35.49 kDa. Based on docking experiments, molecular dynamics simulations, and tertiary structure validation, the analysis of the modeled protein indicates that it possesses a stable structure and can interact with Toll-like receptors. The analysis demonstrates that the proposed vaccine can provoke an immunological response by activating T and B cells, as well as stimulating the release of IgA and IgG antibodies. This vaccine shows potential for HIV-1 prophylaxis. The in-silico design suggests that multiple-epitope constructs can be used as potentially effective immunogens for HIV-1 vaccine development.

Chitosan-nanoparticle-based oral Salmonella enteritidis subunit vaccine elicits cross-protection against Salmonella typhimurium in broilers

Non-typhoidal Salmonella infection is a significant health and economic burden in poultry industry. Developing an oral vaccine to induce robust mucosal immunity in the intestines of birds, especially cross protection against different Salmonella serotypes is challenging. Therefore, a potent oral vaccine platform that can mitigate different serotypes of Salmonella is warranted for the poultry industry. We reported earlier that the Salmonella enteritidis (SE) immunogenic outer membrane proteins (OMPs) and flagellin (FLA) entrapped in mannose chitosan nanoparticles (OMPs-FLA-mCS NPs) administered prime-boost (d-3 and 3-wk later) by oral inoculation elicits mucosal immunity and reduces challenge SE colonization by over 1 log10 CFU in birds. In this study, we sought to evaluate whether the SE antigens containing OMPs-FLA-mCS NPs vaccine induces cross-protection against Salmonella typhimurium (ST) in broilers. Our data indicated that the OMPs-FLA-mCS NPs vaccine induced higher cross-protective antibody responses compared to commercial Poulvac ST vaccine (contains a modified-live ST bacterium). Particularly, OMPs-FLA-mCS-NP vaccine elicited OMPs and FLA antigens specific increased production of secretory IgA and IgY antibodies in samples collected at both post-vaccination and post-challenge timepoints compared to commercial vaccine group. Notably, the vaccine reduced the challenge ST bacterial load by 0.8 log10 CFU in the cecal content, which was comparable to the outcome of Poulvac ST vaccination. In conclusion, our data suggested that orally administered OMPs-FLA-mCS-NP SE vaccine elicited cross protective mucosal immune responses against ST colonization in broilers. Thus, this candidate vaccine could be a viable option replacing the existing both live and killed Salmonella vaccines for birds.

The subdued post-boost spike-directed secondary IgG antibody response in Ugandan recipients of the Pfizer-BioNTech BNT162b2 vaccine has implications for local vaccination policies.

This study aimed to delineate longitudinal antibody responses to the Pfizer-BioNTech BNT162b2 COVID-19 vaccine within the Ugandan subset of the Sub-Saharan African (SSA) demographic, filling a significant gap in global datasets. We enrolled 48 participants and collected 320 specimens over 12 months after the primary vaccination dose. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA antibody concentrations (ng/ml) and optical densities (ODs). Statistical analyses included box plots, diverging bar graphs, and the Wilcoxon test with Bonferroni correction. We noted a robust S-IgG response within 14 days of the primary vaccine dose, which was consistent with global data. There was no significant surge in S-IgG levels after the booster dose, contrasting trends in other global populations. The S-IgM response was transient and predominantly below established thresholds for this population, which reflects its typical early emergence and rapid decline. S-IgA levels rose after the initial dose then decreased after six months, aligning with the temporal patterns of mucosal immunity. Eleven breakthrough infections were noted, and all were asymptomatic, regardless of the participants' initial S-IgG serostatus, which suggests a protective effect from vaccination. The Pfizer-BioNTech BNT162b2 COVID-19 vaccine elicited strong S-IgG responses in the SSA demographic. The antibody dynamics distinctly differed from global data highlighting the significance of region-specific research and the necessity for customised vaccination strategies.

Decoration of Burkholderia Hcp1 protein to virus-like particles as a vaccine delivery platform.

Virus-like particles (VLPs) are protein-based nanoparticles frequently used as carriers in conjugate vaccine platforms. VLPs have been used to display foreign antigens for vaccination and to deliver immunotherapy against diseases. Hemolysin-coregulated proteins 1 (Hcp1) is a protein component of the Burkholderia type 6 secretion system, which participates in intracellular invasion and dissemination. This protein has been reported as a protective antigen and is used in multiple vaccine candidates with various platforms against melioidosis, a severe infectious disease caused by the intracellular pathogen Burkholderia pseudomallei. In this study, we used P22 VLPs as a surface platform for decoration with Hcp1 using chemical conjugation. C57BL/6 mice were intranasally immunized with three doses of either PBS, VLPs, or conjugated Hcp1-VLPs. Immunization with Hcp1-VLPs formulation induced Hcp1-specific IgG, IgG1, IgG2c, and IgA antibody responses. Furthermore, the serum from Hcp1-VLPs immunized mice enhanced the bacterial uptake and opsonophagocytosis by macrophages in the presence of complement. This study demonstrated an alternative strategy to develop a VLPs-based vaccine platform against Burkholderia species.

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral vaccine adjuvant delivery enhancing both the mucosal and systemic immunity

Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer's patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.

Comparison of immunological and molecular methods for laboratory diagnosis of ocular toxoplasmosis in blood, serum and tears in Brazil.

Ocular toxoplasmosis (OT) is caused by protozoan T. gondii. Ophthalmological examination is considered the gold standard for OT diagnosis, and laboratory tests are used for diagnostic confirmation. However, these tests can present different results, which change depending on their basis, on sample type and on patients' clinical alteration. Thus, the aim of the present study is to assess immunodiagnostic and molecular techniques applied in blood, serum and tear fluid to diagnose T. gondii infection in patients seen at an Ophthalmology Clinic. In total, 160 patients were included in the study, 40 of them had OT with active lesions (G1); 40 had OT with healed lesions (G2), 40 had non-toxoplasmic uveitis (G3) and 40 had no ocular alterations (G4). Serum samples were subjected to Immunoenzymatic Assay (ELISA) and to Indirect Immunofluorescence Reaction (IFAT) to search for anti-T. gondii IgM and IgG. Tear fluid samples were analyzed through ELISA for IgA research. All blood and tear fluid samples were subjected to conventional polymerase chain reaction (cPCR) and in a Nested PCR model for T. gondii DNA amplification with targets B1, GRA7 and REP 529. IgG and IgM anti-T. gondii was detected in serum samples from 106 and 15 patients, respectively, when combining ELISA and IFAT results. Anti-T.gondii IgA antibodies were detected in 9.2% of the tear material. Nested PCR with GRA7 target showed higher positivity in blood samples (24.4%); Nested PCR with B1 target showed a higher frequency of positivity in tears (15%). Biological samples of patients with active lesions showed the highest positivity frequencies in all immunodiagnostic assays, as well as in most PCR models. The present results highlighted the need of associating techniques with different fundamentals to confirm OT diagnosis. Furthermore, further tear fluid analyses should be performed to validate this biological material as lesser invasive alternative for the more accurate OT diagnosis.

Anticardiolipin Antibody Plays a More Important Role Than Anti-β2-Glycoprotein I Antibody in Activating Complement in Patients with Lupus Nephritis.

This research aimed to explore the correlation between antiphospholipid antibodies (aPLs) and complement activation in lupus nephritis (LN) patients. A retrospective analysis was carried out on patients diagnosed with LN based on renal biopsy from June 2019 to June 2022. The study assessed levels of IgM, IgA, and IgG subtypes of anticardiolipin antibodies (aCLs) and anti-β2-glycoprotein I (anti-β2-GPI) antibodies. Pathological and clinical data were collected concurrently with the renal biopsy. The analysis included 76 LN patients, with 44.7% testing positive for aPLs. LN patients with positive aPLs exhibited increased hematuria, higher SLEDAI scores, reduced serum C3 and C4 levels, and more C1q deposits in the glomerulus compared to those with negative aPLs (P<0.05). Correlation analysis demonstrated the inverse relationships between IgG-aCL levels and serum C3 and C4 levels (r=-0.29, P=0.005; r=-0.24, P=0.016, respectively), as well as a positive correlation with C4 deposits in the glomerulus (r=0.20, P=0.041). This investigation suggests that aPLs, particularly IgG-aCLs, may be associated with the severity of LN and could contribute to the activation of classical complement pathways.

Antibody Profiling of Pan-Cancer Viral Proteome Reveals Biomarkers for Nasopharyngeal Carcinoma Diagnosis and Prognosis

Diagnosing, predicting disease outcome, and identifying effective treatment targets for virus-related cancers are lacking. Protein biomarkers have the potential to bridge the gap between prevention and treatment for these types of cancers. While it has been shown that certain antibodies against EBV proteins could be used to detect nasopharyngeal carcinoma (NPC), antibodies targeting are solely a tiny part of the about 80 proteins expressed by the EBV genome. Furthermore, it remains unclear what role other viruses play in NPC since many diseases are the result of multiple viral infections. For the first time, this study measured both IgA and IgG antibody responses against 646 viral proteins from 23 viruses in patients with NPC and control subjects using nucleic acid programmable protein arrays. Candidate seromarkers were then validated by ELISA using 1665 serum samples from three clinical cohorts. We demonstrated that the levels of five candidate seromarkers (EBV-BLLF3-IgA, EBV-BLRF2-IgA, EBV-BLRF2-IgG, EBV-BDLF1-IgA, EBV-BDLF1-IgG) in NPC patients were significantly elevated than controls. Additional examination revealed that NPC could be successfully diagnosed by combining the clinical biomarker EBNA1-IgA with the five anti-EBV antibodies. The sensitivity of the six-antibody signature at 95% specificity to diagnose NPC was comparable to the current clinically-approved biomarker combination, VCA-IgA, and EBNA1-IgA. However, the recombinant antigens of the five antibodies are easier to produce and standardize compared to the native viral VCA proteins. This suggests the potential replacement of the traditional VCA-IgA assay with the 5-antibodies combination to screen and diagnose NPC. Additionally, we investigated the prognostic significance of these seromarkers titers in NPC. We showed that NPC patients with elevated BLLF3-IgA and BDLF1-IgA titers in their serum exhibited significantly poorer disease-free survival, suggesting the potential of these two seromarkers as prognostic indicators of NPC. These findings will help develop serological tests to detect and treat NPC in the future.

Sustained S-IgG and S-IgA antibodies to Moderna's mRNA-1273 vaccine in a Sub-Saharan African cohort suggests need for booster timing reconsiderations.

This study sought to elucidate the long-term antibody responses to the Moderna mRNA-1273 COVID-19 vaccine within a Ugandan cohort, aiming to contribute to the sparse data on m-RNA vaccine immunogenicity in Sub-Saharan Africa. We tracked the development and persistence of the elicited antibodies in 19 participants aged 18 to 67, who received two doses of the mRNA-1273 vaccine. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA antibodies against the spike (S) and nucleoproteins (N). The study's temporal scope extended from the baseline to one year, capturing immediate and long-term immune responses. Statistical analyses were performed using the Wilcoxon test to evaluate changes in antibody levels across predetermined intervals with the Hochberg correction for multiple comparisons. Our results showed a significant initial rise in spike-directed IgG (S-IgG) and spike-directed IgA (S-IgA) levels, which remained elevated for the duration of the study. The S-IgG concentrations peaked 14 days afterboosting, while spike-directed IgM (S-IgM) levels were transient, aligning with their early response role. Notably, post-booster antibody concentrations did not significantly change. Prior S-IgG status influenced the post-priming S-IgA dynamics, with baseline S-IgG positive individuals maintaining higher S-IgA responses, a difference that did not reach statistical difference post-boost. Three instances of breakthrough infections: two among participants who exhibited baseline seropositivity for S-IgG, and one in a participant initially seronegative for S-IgG. In conclusion, the mRNA-1273 vaccine elicited robust and persistent S-IgG and S-IgA antibody responses, particularly after the first dose, indicating potential for long-term immunity. Prior viral exposure enhances post-vaccination S-IgA responses compared to naive individuals, which aligned with the prior-naïve, post-boost. The stable antibody levels observed post-booster dose, remaining high over an extended period, with no significant secondary rise, and no difference by baseline exposure, suggest that initial vaccination may sufficiently prime the immune system for prolonged protection in this population, allowing for potential to delay booster schedules as antibody responses remained high at the time of boosting. This finding calls for a reassessment of the booster dose scheduling in this demographic.

Diagnostic accuracy of a novel point-of-care test for simultaneous detection of anti-transglutaminase IgA and anti-deamidated gliadin IgG antibodies.

Point-of-care tests (POCTs) may have a role in detecting undiagnosed cases of Celiac disease (CD). We assessed the diagnostic accuracy of a novel POCT, compared with the conventional serological methods, for simultaneous anti-transglutaminase (tTG) IgA and anti-deamidated gliadin (DGP) IgG antibody detection. Furthermore, we evaluated the effect of different biological matrices (whole blood and serum) on test performance. Serum and whole blood from celiac or suspected celiac patients who underwent duodenal biopsy were assayed for the presence of anti-tTG IgA and anti-DGP IgG both with the reference standard methods (Thermo Fisher Scientific, Uppsala, Sweden) and with the POCT (PRIMA Lab SA, Balerna, Switzerland). 266 sera (101 negative and 165 positive) and 60 whole blood samples (34 positive and 26 negative) were included in the study. POCT for anti-DGP IgG showed a sensitivity of 84.3% and a specificity of 90.1%, with positive (PPV) and negative predictive values (NPV) of 91.07% and 82.73%. POCT for anti-tTG IgA showed a sensitivity of 98.31% and a specificity of 98.02%, with a PPV and NPV of 98.31% and 98.02%. Test accuracies were 86.94% and 98.17%, respectively. The agreement of the results between the two different matrices showed a strong correlation rate: 95% for anti-DGP IgG and 100% for anti-tTG IgA. The anti-tTG IgA/anti-DGP IgG-based POCT showed good diagnostic accuracy with comparable sensitivities and specificities to reference standard methods in detecting CD in symptomatic patients and could be considered as a mass screening test before referring to conventional serology.

Long-Term Kinetics of SARS-CoV-2 Neutralizing and Anti-Receptor Binding Domain Antibodies among Laboratory-Confirmed COVID-19 Cases in Delhi National Capital Region, India: A Prospective, One-Year Follow-Up Study.

Background: This study was conducted with the objective of measuring the neutralizing and anti-receptor binding domain antibody levels against SARS-CoV-2 among laboratory-confirmed COVID-19 cases and exploring its long-term kinetics over a period of 1 year. Methods: One hundred laboratory-confirmed COVID-19 cases were recruited. Serum samples of the participants were collected within three months from the date of the positive COVID-19 report. The participants were prospectively followed up every three months for symptoms and the collection of blood samples for three additional rounds. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG, and IgM antibodies), anti-receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Median plaque reduction neutralization test (PRNT) titers showed a rising trend in the first three rounds of follow-up. The quantitative anti-receptor binding domain ELISA (QRBD) values showed a declining trend in the initial three rounds. However, both the PRNT titers and QRBD values showed significantly higher values for the fourth round of follow-up. Total antibody (WANTAI) levels showed an increasing trend in the initial three rounds (statistically significant). Interpretation: Neutralizing antibodies showed an increasing trend. The anti-receptor binding domain antibodies showed a decreasing trend. Neutralizing antibodies and anti-RBD antibodies persisted in the majority.

Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2

Passive delivery of antibodies to mucosal sites might be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralising monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred, as the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralising monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralisation activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

Immunogenicity and protective efficacy of a trimeric full-length S protein subunit vaccine for porcine epidemic diarrhea virus

Porcine epidemic diarrhea virus (PEDV) has caused serious economic losses to the pig husbandry worldwide, and the effects of existing commercialized vaccines are suboptimal. Therefore, research to develop an efficacious vaccine for prevention and control of PEDV is essential. In this study, we designed and produced trimerized proteins of full-length PEDV spike (S) protein, S1 subunit, and a tandem of multiple epitopes of S protein using an efficient mammalian expression vector system in HEK 293F cells. The immunogenicity of two commercial adjuvants, M401 and M103, was also evaluated in mice. Enzyme-linked immunosorbent assays demonstrated that all immunized mice generated highly systemic PEDV S-specific IgG and IgA antibodies. Mice in S/M103-immunized group generated the highest neutralizing antibody titer with 1:96. Compared with control group, the subunit vaccines elicited multifunctional CD3+CD4+ and CD3+CD8+ T cells, B220+CD19+ B cells, and CD3-CD49b+ natural killer cells in the spleen. PEDV S/M103 vaccine, which had the best immune effect, was selected for further evaluation in piglets. Immunization with S/M103 vaccine induced high levels of S-specific IgG, IgA, and neutralizing antibodies, and increased the proliferation of peripheral blood mononuclear cells and the expression levels of interferon-γ and interleukin-4 in peripheral blood of piglets. Virus challenge test results showed significantly lower diarrheal index scores and fecal viral loads, and less pathological damage to the intestines in S/M103-immunized piglets than in controls, indicating that S/M103 provides good protection against the virulent virus challenge. Our findings suggest that trimeric PEDV S/M103 has potential as a clinical vaccine candidate.

Can the Epstein-Barr Virus Play a Role in the Development of Prostate Cancer?

Prostate cancer (PCa) is the fourth most frequently diagnosed cancer worldwide, accounting for 7.3% of all cancers. PCa mortality is the fifth most common cause of cancer death. Despite well-known factors influencing the development of PCa, such as age, race/ethnicity and family history, many researchers have raised the possibility of persistent infections with oncogenic viruses. Therefore, we aimed to assess the frequency of Epstein-Barr virus (EBV) DNA in tissue collected from PCa patients. Next, the frequency and the level of Epstein-Barr virus capsid antigen (EBVCA) and Epstein-Barr nuclear antigen 1 (EBNA1) antibodies in both IgA and IgG classes were measured. The antibody titer was also analyzed depending on the risk group, Gleason score (GS) and tumor, node, metastasis (TNM) classification. Serum samples were analyzed using the Microblot-Array EBV IgM, IgA and IgG test kits. The study group consisted of 115 patients diagnosed and histopathologically confirmed with PCa. In 49% of patients included in the study, EBV DNA was detected in the tumor tissue. The studies showed both higher seroprevalence and higher antibody titers in patients with EBV-positive PCa compared to patients with EBV-negative PCa. We also observed a dependence of antibody titer on pathological features, such as GS, risk group and T stage.

Preparation and activity study of Ruoqiang jujube polysaccharide copper chelate.

Background: Polysaccharide metal chelate exhibit both immunoregulatory activity and metal element supplementation effects. Methods: In this study, Ruoqiang jujube polysaccharide copper chelate (RJP-Cu) was prepared and the preparation conditions were optimized using the response surface method. Subsequently, RJP-Cu was administered to lambs to evaluate its impact on growth performance, copper ion (Cu2+) supplementation, immune enhancement, and intestinal flora was evaluated. Results: The results indicated that optimal RJP-Cu chelation conditions included a sodium citrate content of 0.5 g, a reaction temperature of 50°C, and a solution pH of 8.0, resulting in a Cu2+ concentration of 583°mg/kg in RJP-Cu. Scanning electron microscopy (SEM) revealed significant structural changes in RJP before and after chelation. RJP-Cu displaying characteristic peaks of both polysaccharides and Cu2+ chelates. Blood routine indexes showed no significant differences among the RJP-Cu-High dose group (RJP-Cu-H), RJP-Cu-Medium dose group (RJP-Cu-M), RJP-Cu-low dose group (RJP-Cu-L) and the control group (p > 0.05). However, compared with the control group, the RJP-Cu-H, M, and L dose groups significantly enhanced lamb production performance (p < 0.05). Furthermore, RJP-Cu-H, M, and L dose groups significantly increased serum Cu2+ concentration, total antioxidant capacity (T-AOC), catalase (CAT), and total superoxide dismutase (T-SOD) contents compared with control group (p < 0.05). The RJP-Cu-H group exhibited significant increases in serum IgA and IgG antibodies, as well as the secretion of cytokines IL-2, IL-4, and TNF-α compared to the control group (p < 0.05). Furthermore, RJP-Cu-H group increased the species abundance of lamb intestinal microbiota, abundance and quantity of beneficial bacteria, and decrease the abundance and quantity of harmful bacteria. The RJP-Cu-H led to the promotion of the synthesis of various Short Chain Fatty Acids (SCFAs), improvements in atrazine degradation and clavulanic acid biosynthesis in lambs, while reducing cell apoptosis and lipopolysaccharide biosynthesis. Conclusion: Thus, these findings demonstrate that RJP-Cu, as a metal chelate, could effectively promote lamb growth performance, increase Cu2+ content, and potentially induce positive immunomodulatory effects by regulating antioxidant enzymes, antibodies, cytokines, intestinal flora, and related metabolic pathways.

Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages.

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot sufficiently boost the mucosal secretory IgA response in uninfected individuals, particularly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgA1 antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibodies, dimeric and secretory IgA1 antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgA1 form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secretory IgA delivered by nasal administration may potentially be exploited for the treatment and prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.