Cellular response, persistent humoral response and efficacy elicited by a CV-A16 vaccine candidate in mice

Coxsackievirus A16 (CV-A16) is a major pathogen of hand, foot and mouth disease (HFMD). To control HFMD, a CV-A16 vaccine is needed. In this study, the immunogenicity and efficacy of an inactivated CV-A16 vaccine were evaluated in mice. The inactivated CV-A16 vaccine induced effective neutralizing antibodies and T cell responses in BALB/c mice after two doses of intraperitoneal inoculation. The duration of neutralizing antibody and memory B cell persisted for up to 6 months. Four T cell epitopes locating at the VP1 and VP3 were identified for the first time to be CV-A16-specific in mice. A mouse-adapted CV-A16 strain was used to evaluate the efficacy of the CV-A16 vaccine in preventing the death of 14-day-old mice. In an actively immunized-challenged system, the neonatal Kunming mice were intraperitoneally inoculated with the CV-A16 vaccine at doses of 0.1 μg, 0.5 μg or 2.5 μg on days 3 and 9, followed by challenge on day 14. The anti-CV-A16 mouse sera elicited by vaccination showed a high level of neutralizing antibodies against homologous CV-A16 strain. The protective rates of mice immunized with 0.1 μg, 0.5 μg or 2.5 μg vaccine were 90 %, 100 % and 100 %, respectively. In contrast, all mice in the Alum-inoculated group developed paralysis of both hindlimbs and died at 3 days post-challenge, which exhibited high viral loads, severe pathological damages and strong viral protein expression. These results indicated that the inactivated CV-A16 vaccine is promising and that the mouse model will be useful for studying CV-A16 pathogenesis and further evaluation in a multivalent vaccine including the CV-A16 candidate.