Poorly neutralizing polyclonal antibody in vitro against coxsackievirus A16 circulating strains can prevent a lethal challenge in vivo

Abstract

Neutralizing antibodies (NTAbs) is a major criterion for evaluation the immunogenicity of many vaccines, for example, poliovirus and EV71 vaccine. Here, we firstly discovered that polyclonal antibodies induced by inactivated CVA16 vaccine and lived CVA16 virus have poor ability to neutralize circulating CVA16 strains in vitro. However, the passive transfer of poorly neutralizing polyclonal antibodies can protect suckling mice from lethally challenged with circulating strains in vivo. In addition, the obvious dose response was found between the titer of antibodies and the survival rate. Interestingly, poorly neutralizing polyclonal antibodies against circulating CVA16 strains, have good ability to neutralize prototype strain G10 in vitro. Between G10 and circulating CVA16 strains, there are total 47 variant sites in capsid, which are near the interface of VP1, VP2, and VP3, and close to 2-fold axis. Based on the structure of CVA16, the obvious structural changes were observed in residue 213 of VP1 GH loop, residue 139 of VP2 EF loop, and residues 59, 182 and 183 of VP3 GH loop. What we found may provide a new sight for the development of CVA16 vaccine.

Keywords

• coxsackievirus a16
• hand foot and mouth disease
• neutralizing epitopes
• structure
• vaccine