Enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and CV-A10 belong to the main prevailing types causing hand-foot-and-mouth disease. Since EV-A71 monovalent vaccine does not confer cross-protection, developing a multivalent vaccine is essential. In this study, a trivalent chimeric virus-like particle of EV-A71 (EV-A71-VLPCHI3) was constructed based on EV-A71-VLP backbone by replacing the corresponding surface loops with CV-A16 VP1 G-H, CV-A10 VP1 B-C and E-F loops, which are critical for immunogenic neutralization. The baculovirus-insect cell expression system was employed for EV-A71-VLPCHI3 production. EV-A71-VLPCHI3 was purified by sucrose density gradient and observed by transmission electron microscopy. The immunogenicity and protective efficacy of EV-A71-VLPCHI3 were evaluated in mice. Our results revealed that EV-A71-VLPCHI3 had a similar morphology to inactivated EV-A71 particles and could induce specific IgG antibodies against EV-A71, CV-A16 and CV-A10 in mice. More importantly, EV-A71-VLPCHI3 enhanced cross-reactive protection against CV-A16 and CV-A10, by 20 % and 40 %, compared to inactivated EV-A71 counterparts, respectively. In conclusion, the successful construction of EV-A71-VLPCHI3 suggested that loop-dependent heterologous protection could be transferred by loops replacement on the surface of viral capsid. This strategy may also supplement the development of multivalent vaccines against other infectious viral diseases.
Keywords: Chimeric vaccine; Enterovirus; Hand-foot-and-mouth disease; Virus-like particle.
Copyright © 2023. Published by Elsevier B.V.