Key result
VP1-141 substitution drives CVA10 Vero cell infectivity and strong immunogenicity for vaccine development.
Why the study?
Most clinical isolates of CVA10 are difficult to propagate in Vero cells, hindering the development of vaccines for hand, foot, and mouth disease.
Identification of the VP1-141 substitution as critical for Vero cell adaptation of CVA10 provides a foundation for developing multivalent hand, foot, and mouth disease vaccines.
May inform Vero-adapted CVA10 vaccine design; leaves open human immunogenicity and efficacy.
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.
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Chen et al. (2026) studied Hand, foot, and mouth diseases (HFMD). Vero cell-adapted CVA10 strain (CVA10-V) vs. RD-propagated CVA10 strain (CVA10-R) / empty-particle was evaluated on Vero cell infectivity and immunogenicity in mice. Substitution of D from E at position VP1–141 is the critical determinant for CVA10-V infection of Vero cells, enabling strong immunogenicity for vaccine development.
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