VP1-141 is a determinant of a Vero cell-adapted Coxsackievirus A10 for vaccine development.

Coxsackievirus A10 (CVA10) infection primarily causes hand, foot, and mouth diseases (HFMD) in children. As CVA10 is one of the most widespread enteroviruses, the development of a CVA10 vaccine is essential. It could also be used to create a multivalent vaccine for preventing HFMD alongside other enteroviruses. Most clinical isolates of CVA10 are difficult to propagate in Vero cells, while only a few pre-screened CVA10 clones could. In this study, we have successfully isolated a highly Vero cell-adapted CVA10 strain (CVA10-V) from the parental CVA10. After propagation of CVA10-V in Vero cells, the purified full-particle (F-particle) of CVA10-V could induce strong immunogenicity in mice model, while the empty-particle of CVA10-V did not. The CVA10-V F-particle were mixed with EV-A71 bulk for immunization and a good neutralization response to each virus were observed. In this study, a RD-propagated CVA10 strain (CVA10-R) was not unable to infect Vero cells. Five amino acid variations of P1 protein (470, 664, 705, 792, and 804) were noted between the CVA10-V and CVA10-R. Infectious clones with single-site mutation representing these five locations were constructed to investigate the effects of these variations on Vero infectivity. Substitution of D from E at position VP1-141 (P1-705) was found to be the critical determinant for CVA10-V infection of Vero cells. Variation at this position was found to affect CVA10's ability to attach to Vero cells. Our study pinpoints the critical sites of viral P1 protein that render the Vero-adaptation and this Vero-adapted CVA10-V strain would be beneficial for multivalent HFMD vaccine development using the Vero cell culture system.