Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine

Ziyan Meng; Danjing Ma; Suqin Duan; Jingjing Zhang; Rong Yue; Xinghang Li; Yang Gao; Xueqi Li; Fengyuan Zeng; Xiangxiong Xu; Guorun Jiang; Yun Liao; Shengtao Fan; Zhenye Niu; Dandan Li; Li Yu; Heng Zhao; Xingli Xu; Lichun Wang; Ying Zhang; Longding Liu; Qihan Li

doi:10.3390/vaccines10060929

Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine

Vaccines (Basel). 2022 Jun 10;10(6):929. doi: 10.3390/vaccines10060929.

Authors

Ziyan Meng¹, Danjing Ma¹, Suqin Duan¹, Jingjing Zhang¹, Rong Yue¹, Xinghang Li¹, Yang Gao¹, Xueqi Li¹, Fengyuan Zeng¹, Xiangxiong Xu¹, Guorun Jiang¹, Yun Liao¹, Shengtao Fan¹, Zhenye Niu¹, Dandan Li¹, Li Yu¹, Heng Zhao¹, Xingli Xu¹, Lichun Wang¹, Ying Zhang¹, Longding Liu¹, Qihan Li¹

Affiliation

¹ Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.

Abstract

Objective: We 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. Methods: Two 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. Results: The 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. Conclusion: The 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.

Keywords: COVID-19; DNA vaccine; RBD; SARS-CoV-2; inactivated vaccine; variants.

Abstract

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