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Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice.

ABSTRACT: The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, administered via both intranasal and intramuscular routes in BALB/c mice. Intramuscular priming followed by an intranasal booster elicited the highest levels of IgG, IgA, and pseudovirus neutralizing antibody titres among all the protocols tested at day 42 after prime immunization compared with the intranasal priming/intramuscular booster and prime-boost protocols using only one route. In addition, intramuscular priming followed by an intranasal booster induced high T-cell responses, measured using the IFN-γ ELISpot assay, that were similar to those observed upon intramuscular vaccination. All ChAdTS-S vaccination groups induced Th1-skewing of the T-cell response according to intracellular cytokine staining and Meso Scale Discovery cytokine profiling assays on day 56 after priming. This study provides reference data for assessing vaccination schemes of adenovirus-based COVID-19 vaccines with high immune efficacy.

SUBMITTER: Li X

PROVIDER: S-EPMC9331206 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice.

Li Xingxing X Wang Ling L Liu Jingjing J Fang Enyue E Liu Xiaohui X Peng Qinhua Q Zhang Zelun Z Li Miao M Liu Xinyu X Wu Xiaohong X Zhao Danhua D Yang Lihong L Li Jia J Cao Shouchun S Huang Yanqiu Y Shi Leitai L Xu Hongshan H Wang Yunpeng Y Suo Yue Y Yue Guangzhi G Nie Jianhui J Huang Weijin W Li Wenjuan W Li Yuhua Y

Emerging microbes & infections 20221201 1

The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, ad ...[more]

PMID: 35775819

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Project description:BackgroundA three-antigen DNA-prime/chimpanzee adenovirus 63 (ChAd63) boost vaccine containing pre-erythrocytic Plasmodium falciparum (Pf) circumsporozoite protein (CSP), Pf apical membrane antigen-1 (AMA1) and malaria multiple epitopes (ME) fused to Pf thrombospondin-related adhesion protein (ME-TRAP) elicited higher vaccine efficacy (VE) in an open label, randomized Phase 1 trial against controlled human malaria infection (CHMI) than the two-antigen vaccine DNA/Human Adenovirus 5 (HuAd5) containing CSP and AMA1. The objective of this follow-up study was to determine whether responses to CSP, AMA1 or TRAP MHC Class I-restricted epitopes were associated with VE.MethodologyProtected (n = 6) and non-protected participants (n = 26) were screened in FluoroSpot interferon gamma (IFN-γ) and Granzyme B (GzB) assays using antigen-specific 15mer peptide subpools spanning CSP (n = 9 subpools), AMA1 (n = 12 subpools), and TRAP (n = 11 subpools). Individual antigen-specific 15mers in the subpools with strong responses were then deconvoluted, evaluated for activities, and MHC Class I-restricted epitopes within the active 15mers were predicted using NetMHCpan algorithms. The predicted epitopes were synthesized and evaluated in the FluoroSpot IFN-γ and GzB assays.ResultsProtected and some non-protected participants had similar responses to individual antigen-specific peptide subpools, which did not distinguish only protected participants. However, deconvoluted antigen-specific positive subpools with high magnitudes of responses revealed individual 15mer peptides containing specific and/or predicted MHC Class I (HLA) epitopes. Responses to epitopes were either IFN-γ-only, IFN-γ and GzB, or GzB-only. Due to limitation of cells, most of the analysis concentrated on the identification of protection associated AMA1 epitopes, since most of the predominant pool specific responses were generated against AMA1 15mer subpools. Furthermore, we previously identified protection associated HLA class I-restricted epitopes in a previous gene-based vaccine trial. Seven predicted minimal epitopes in AMA1 were synthesized and upon testing, five recalled responses from protected participants confirming their possible contribution and association with protection, and two recalled responses from non-protected participants. Two protection-associated epitopes were promiscuous and may have also contributed to protection by recognition of different HLA alleles. In addition, strongly positive antigen-specific 15mers identified within active antigen-specific subpools contained 39 predicted but not tested epitopes were identified in CSP, AMA1 and TRAP. Finally, some non-protected individuals recognized HLA-matched protection-associated minimal epitopes and we discuss possible reasons. Other factors such as HLA allele fine specificity or interaction between other HLA alleles in same individual may also influence protective efficacy.ConclusionsThis integrated approach using immunoassays and bioinformatics identified and confirmed AMA1-MHC Class I-restricted epitopes and a list of predicted additional epitopes which could be evaluated in future studies to assess possible association with protection against CHMI in the Phase 1 trial participants. The results suggest that identification of protection-associated epitopes within malaria antigens is feasible and can help design potent next generation multi-antigen, multi-epitope malaria vaccines for a genetically diverse population and to develop robust assays to measure protective cellular immunity against pre-erythrocytic stages of malaria. This approach can be used to develop vaccines for other novel emerging infectious disease pathogens.

Dataset Information

Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice.

Publications

Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice.

Similar Datasets

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