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Different T-cell and B-cell repertoire elicited by the SARS-CoV-2 inactivated vaccine and S1 subunit vaccine in rhesus macaques.

ABSTRACT: Multiple types of SARS-CoV-2 vaccines have been used worldwide, but summarizing their immunologic efficacy post-vaccination remains challenging. The BCR and TCR sequencing based on single-cell sorting makes it possible to evaluate the vaccine-induced immune responses of B or T cells. In this study, we compared the repertoire diversities of B cells and T cells between a whole-virus inactivated vaccine and an S1 protein subunit vaccine in rhesus macaques. We found that the inactivated vaccine could induce a large antigen-specific-BCR repertoire with longer VH CDR3 (21 aa), while the CD3+ TCR α chains of the two vaccine groups showed a similar TCRV/J usage frequency. Detailed analysis of the TCR and BCR repertoires might be of interest for further understanding of the mechanisms of vaccine-induced immune responses.

SUBMITTER: Qin L

PROVIDER: S-EPMC9746386 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Different T-cell and B-cell repertoire elicited by the SARS-CoV-2 inactivated vaccine and S1 subunit vaccine in rhesus macaques.

Qin Li L Zuo Yuanyuan Y Liu Shuying S Li Bingxiang B Wang Hongye H Li Heng H Li Jing J Chen Yanli Y Sun Ming M Zheng Huiwen H

Human vaccines & immunotherapeutics 20220907 6

Multiple types of SARS-CoV-2 vaccines have been used worldwide, but summarizing their immunologic efficacy post-vaccination remains challenging. The BCR and TCR sequencing based on single-cell sorting makes it possible to evaluate the vaccine-induced immune responses of B or T cells. In this study, we compared the repertoire diversities of B cells and T cells between a whole-virus inactivated vaccine and an S1 protein subunit vaccine in rhesus macaques. We found that the inactivated vaccine coul ...[more]

PMID: 36070519

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Project description:UnlabelledDespite significant progress in reducing peripartum mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) with antiretroviral therapy (ART), continued access to ART throughout the breastfeeding period is still a limiting factor, and breast milk exposure to HIV accounts for up to 44% of MTCT. As abstinence from breastfeeding is not recommended, alternative means are needed to prevent MTCT of HIV. We have previously shown that oral vaccination at birth with live attenuated Mycobacterium tuberculosis strains expressing simian immunodeficiency virus (SIV) genes safely induces persistent SIV-specific cellular and humoral immune responses both systemically and at the oral and intestinal mucosa. Here, we tested the ability of oral M. tuberculosis vaccine strains expressing SIV Env and Gag proteins, followed by systemic heterologous (MVA-SIV Env/Gag/Pol) boosting, to protect neonatal macaques against oral SIV challenge. While vaccination did not protect infant macaques against oral SIV acquisition, a subset of immunized animals had significantly lower peak viremia which inversely correlated with prechallenge SIV Env-specific salivary and intestinal IgA responses and higher-avidity SIV Env-specific IgG in plasma. These controller animals also maintained CD4(+) T cell populations better and showed reduced tissue pathology compared to noncontroller animals. We show that infants vaccinated at birth can develop vaccine-induced SIV-specific IgA and IgG antibodies and cellular immune responses within weeks of life. Our data further suggest that affinity maturation of vaccine-induced plasma antibodies and induction of mucosal IgA responses at potential SIV entry sites are associated with better control of viral replication, thereby likely reducing SIV morbidity.ImportanceDespite significant progress in reducing peripartum MTCT of HIV with ART, continued access to ART throughout the breastfeeding period is still a limiting factor. Breast milk exposure to HIV accounts for up to 44% of MTCT. Alternative measures, in addition to ART, are needed to achieve the goal of an AIDS-free generation. Pediatric HIV vaccines constitute a core component of such efforts. The results of our pediatric vaccine study highlight the potential importance of vaccine-elicited mucosal Env-specific IgA responses in combination with high-avidity systemic Env-specific IgG in protection against oral SIV transmission and control of viral replication in infant macaques. The induction of potent mucosal IgA antibodies by our vaccine is remarkable considering the age-dependent development of mucosal IgA responses postbirth. A deeper understanding of postnatal immune development may inform the design of improved vaccine strategies to enhance systemic and mucosal SIV/HIV antibody responses.

Project description:IntroductionIt is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques.MethodsWe analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 to impute metagenomic information, and mass spectrophotometry to determine levels of fecal short-chain fatty acids and bile acids.ResultsComposition of the early-life gut microbial communities in nursery-reared rhesus macaques from the same animal care facility was driven by age, birth year, and vaccination status. We identified a Sutterella and a Rodentibacter species that positively correlated with vaccine-elicited antibody responses, with the Sutterella species exhibiting more robust findings. Analysis of Sutterella-related metagenomic data revealed five metabolic pathways that significantly correlated with improved antibody responses following HIV vaccination. Given these pathways have been associated with short-chain fatty acids and bile acids, we quantified the fecal concentration of these metabolites and found several that correlated with higher levels of HIV immunogen-elicited plasma IgG.DiscussionOur findings highlight an intricate bidirectional relationship between the microbiota and vaccines, where multiple aspects of the vaccination regimen modulate the microbiota and specific microbial features facilitate vaccine responses. An improved understanding of this microbiota-vaccine interplay will help develop more effective vaccines, particularly those that are tailored for early life.

Dataset Information

Different T-cell and B-cell repertoire elicited by the SARS-CoV-2 inactivated vaccine and S1 subunit vaccine in rhesus macaques.

Publications

Different T-cell and B-cell repertoire elicited by the SARS-CoV-2 inactivated vaccine and S1 subunit vaccine in rhesus macaques.

Similar Datasets

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