Humoral and cellular immunogenicity and efficacy of a coxsackievirus A10 vaccine in mice

Emerg Microbes Infect. 2023 Dec;12(1):e2147022. doi: 10.1080/22221751.2022.2147022.

Abstract

Coxsackievirus A10 (CV-A10) has become one of the major pathogens of hand, foot and mouth disease (HFMD), and studies on the vaccine and animal model of CV-A10 are still far from complete. Our study used a mouse-adapted CV-A10 strain, which was lethal for 14-day-old mice, to develop an infected mouse model. Then this model was employed to establish an actively immunized-challenged mouse model to evaluate the efficacy of a formaldehyde-inactivated CV-A10 vaccine, which was prepared from a Vero cell-adapted strain. CV-A10 vaccine at a dose of 0.5 or 2.0 μg was inoculated intraperitoneally in neonatal Kunming mice on the third and ninth day. Then the mice were challenged on day 14. The survival rate of mice immunized with 0.5 or 2.0 μg vaccine were 90% and 100%, respectively, while all Alum-inoculated mice died. Compared to those in the two vaccinated groups, the Alum-inoculated mice showed severe pathological damage, strong viral protein expression and high viral loads. The antisera from vaccinated mice showed high level of neutralizing antibodies against CV-A10. Meanwhile, three potential T cell epitopes located at the carboxyl-terminal regions of the VP1 and VP3 were identified and exhibited CV-A10 serotype-specific. The humoral and cellular immunogenicity analysis showed that immunization with two doses of the vaccine elicited CV-A10 specific neutralizing antibody and T cell response in BALB/c mice. Collectively, these findings indicated that this actively immunized-challenged mouse model will be invaluable in future studies on CV-A10 pathogenesis and evaluation of vaccine candidates.

Keywords: CV-A10 vaccine; T cell epitope; active immunization-challenge; efficacy; humoral and cellular immunogenicity; mouse model.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Enterovirus A, Human* / genetics
  • Hand, Foot and Mouth Disease* / prevention & control
  • Mice
  • Vaccines, Inactivated
  • Viral Vaccines*

Substances

  • aluminum sulfate
  • Antibodies, Viral
  • antineoplaston A10
  • Viral Vaccines
  • Antibodies, Neutralizing
  • Vaccines, Inactivated

Supplementary concepts

  • Kunming mice

Grants and funding

This work was supported by the Ministry of Science and Technology of the People’s Republic of China [No.2015ZX09102021].