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

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. Met...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/10/6/929
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author 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
author_facet 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
author_sort Ziyan Meng
collection DOAJ
description 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 (<i>p</i> < 0.001) and 2430 (<i>p</i> < 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.
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spelling doaj.art-e74a186f9f1a4392ac103879e1c173cc2023-11-23T19:21:35ZengMDPI AGVaccines2076-393X2022-06-0110692910.3390/vaccines10060929Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated VaccineZiyan Meng0Danjing Ma1Suqin Duan2Jingjing Zhang3Rong Yue4Xinghang Li5Yang Gao6Xueqi Li7Fengyuan Zeng8Xiangxiong Xu9Guorun Jiang10Yun Liao11Shengtao Fan12Zhenye Niu13Dandan Li14Li Yu15Heng Zhao16Xingli Xu17Lichun Wang18Ying Zhang19Longding Liu20Qihan Li21Yunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaYunnan 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, ChinaObjective: 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 (<i>p</i> < 0.001) and 2430 (<i>p</i> < 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.https://www.mdpi.com/2076-393X/10/6/929SARS-CoV-2COVID-19DNA vaccineinactivated vaccinevariantsRBD
spellingShingle 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
Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine
Vaccines
SARS-CoV-2
COVID-19
DNA vaccine
inactivated vaccine
variants
RBD
title Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine
title_full Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine
title_fullStr Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine
title_full_unstemmed Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine
title_short Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine
title_sort immunological study of combined administration of sars cov 2 dna vaccine and inactivated vaccine
topic SARS-CoV-2
COVID-19
DNA vaccine
inactivated vaccine
variants
RBD
url https://www.mdpi.com/2076-393X/10/6/929
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