Active inoculation with an inactivated Coxsackievirus A2 vaccine induces neutralizing antibodies and protects mice against lethal infection

Yuexia Wang; Wangquan Ji; Dong Li; Tiantian Sun; Peiyu Zhu; Junwei Li; Liang Zhang; Yu Zhang; Haiyan Yang; Shuaiyin Chen; Yuefei Jin; Guangcai Duan

doi:10.1016/j.vaccine.2023.08.083

Active inoculation with an inactivated Coxsackievirus A2 vaccine induces neutralizing antibodies and protects mice against lethal infection

Vaccine. 2023 Oct 13;41(43):6470-6482. doi: 10.1016/j.vaccine.2023.08.083. Epub 2023 Sep 15.

Authors

Yuexia Wang¹, Wangquan Ji², Dong Li², Tiantian Sun², Peiyu Zhu², Junwei Li³, Liang Zhang², Yu Zhang⁴, Haiyan Yang⁴, Shuaiyin Chen⁴, Yuefei Jin⁵, Guangcai Duan⁶

Affiliations

¹ Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China; Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, Henan, China; Department of Infectious Disease Control and Prevention, Jiangshan Center for Disease Control and Prevention, Jiangshan 324100, Zhejiang, China.
² Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China; Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, Henan, China.
³ Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China; Department of Infectious Disease Control and Prevention, Jiangshan Center for Disease Control and Prevention, Jiangshan 324100, Zhejiang, China.
⁴ Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
⁵ Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: jyf201907@zzu.edu.cn.
⁶ Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China; Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: gcduan@zzu.edu.cn.

PMID: 37718187
DOI: 10.1016/j.vaccine.2023.08.083

Abstract

Coxsackievirus A2 (CVA2) is one of the causative agents of hand-foot-and-mouth disease (HFMD), which poses a great challenge for global public health. However, presently, there are no available commercial vaccines or antivirals to prevent CVA2 infection. Here, we present an inactivated Vero cell-based whole CVA2 vaccine candidate and evaluate its safety and efficacy in this study. Neonatal BALB/c mice were vaccinated at 5 and 7 days old, respectively, and then challenged with either homologous or heterologous strain of CVA2 at a lethal dose at 10 days old. The inactivated whole CVA2 vaccine candidate showed a high protective efficacy. Additionally, our inactivated vaccine stimulated the production of CVA2-specific IgG1 and IgG2a antibodies in vivo and high titers of neutralization antibodies (NtAbs) in the serum of immunized mice. Maternal immunization with the inactivated CVA2 vaccine provided full protection to pups against lethal infection. Compared with mice inoculated with only alum, the viral loads were decreased, and pathological changes were relieved in tissue samples of immunized mice. Moreover, the transcription levels of some genes related to cytokines (IFN-γ and TNF-α, MCP-1, IL-6, CXCL-10 etc.) were significantly reduced. The number of immune cells and levels of cytokines in peripheral blood of mice inoculated with only alum were higher than that of immunized mice. It is noteworthy that this vaccine showed a good cross-immunity efficacy against Enterovirus A71 (EVA71) challenge. In conclusion, our findings suggest that this experimental inactivated CVA2 vaccine is a promising component of polyvalent vaccines related to HFMD in the near future.

Keywords: Coxsackievirus A2; Cross immunity; Hand-foot-and-mouth disease; Mouse model; Vaccine.