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Immunological evaluation of an inactivated SARS-CoV-2 vaccine in rhesus macaques.

ABSTRACT: Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

SUBMITTER: Chen H

PROVIDER: S-EPMC8387130 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Immunological evaluation of an inactivated SARS-CoV-2 vaccine in rhesus macaques.

Chen Hongbo H Xie Zhongping Z Long Runxiang R Fan Shengtao S Li Heng H He Zhanlong Z Xu Kangwei K Liao Yun Y Wang Lichun L Zhang Ying Y Li Xueqi X Dong Xingqi X Mou Tangwei T Zhou Xiaofang X Yang Yaoyun Y Guo Lei L Yang Jianbo J Zheng Huiwen H Xu Xingli X Li Jing J Liang Yan Y Li Dandan D Zhao Zhimei Z Hong Chao C Zhao Heng H Jiang Guorun G Che Yanchun Y Yang Fengmei F Hu Yunguang Y Wang Xi X Pu Jing J Ma Kaili K Wang Lin L Cheng Chen C Duan Weiguo W Shen Dong D Zhao Hongling H Jiang Ruiju R Deng Xinqiang X Li Yan Y Zhu Hailian H Zhou Jian J Yu Li L Xu Mingjue M Yang Huijuan H Yi Li L Zhou Zhenxin Z Yang Jiafang J Duan Nan N Yang Huan H Zhao Wangli W Yang Wei W Li Changgui C Liu Longding L Li Qihan Q

Molecular therapy. Methods & clinical development 20210826

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by seq ...[more]

PMID: 34462721

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Project description:ObjectiveWe constructed two DNA vaccines containing the receptor-binding domain (RBD) genes of multiple SARS-CoV-2 variants and used them in combination with inactivated vaccines in a variety of different protocols to explore potential novel immunization strategies against SARS-CoV-2 variants.MethodsTwo DNA vaccine candidates with different signal peptides (namely, secreted and membrane signal peptides) and RBD protein genes of different SARS-CoV-2 strains (Wuhan-Hu-1, B.1.351, B.1.617.2, C.37) were used. Four different combinations of DNA and inactivated vaccines were tested, namely, Group A: three doses of DNA vaccine; B: three doses of DNA vaccine and one dose of inactivated vaccine; C: two doses of inactivated vaccine and one dose of DNA vaccine; and D: coadministration of DNA and inactivated vaccines in two doses. Subgroups were grouped according to the signal peptide used (subgroup 1 contained secreted signal peptides, and subgroup 2 contained membrane signal peptides). The in vitro expression of the DNA vaccines, the humoral and cellular immunity responses of the immunized mice, the immune cell population changes in local lymph nodes, and proinflammatory cytokine levels in serum samples were evaluated.ResultsThe antibody responses and cellular immunity in Group A were weak for all SARS-CoV-2 strains; for Group B, there was a great enhancement of neutralizing antibody (Nab) titers against the B.1.617.2 variant strain. Group C showed a significant increase in antibody responses (NAb titers against the Wuhan-Hu-1 strain were 768 and 1154 for Group C1 and Group C2, respectively, versus 576) and cellular immune responses, especially for variant B.1.617.2 (3240 (p < 0.001) and 2430 (p < 0.05) for Group C1 and Group C2, versus 450); Group D showed an improvement in immunogenicity. Group C induced higher levels of multiple cytokines.ConclusionThe DNA vaccine candidates we constructed, administered as boosters, could enhance the humoral and cellular immune responses of inactivated vaccines against COVID-19, especially for B.1.617.2.

Dataset Information

Immunological evaluation of an inactivated SARS-CoV-2 vaccine in rhesus macaques.

Publications

Immunological evaluation of an inactivated SARS-CoV-2 vaccine in rhesus macaques.

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