Enterovirus virus-like-particle and inactivated poliovirus vaccines do not elicit substantive cross-reactive antibody responses

Human enteroviruses are the most common human pathogen with over 300 distinct genotypes. Previous work with poliovirus has suggested that it is possible to generate antibody responses in humans and animals that can recognize members of multiple enterovirus species. However, cross protective immunity across multiple enteroviruses is not observed epidemiologically in humans. Here we investigated whether immunization of mice or baboons with inactivated poliovirus or enterovirus virus-like-particles (VLPs) vaccines generates antibody responses that can recognize enterovirus D68 or A71. We found that mice only generated antibodies specific for the antigen they were immunized with, and repeated immunization failed to generate cross-reactive antibody responses as measured by both ELISA and neutralization assay. Immunization of baboons with IPV failed to generate neutralizing antibody responses against enterovirus D68 or A71. These results suggest that a multivalent approach to enterovirus vaccination is necessary to protect against enterovirus disease in vulnerable populations. Enteroviruses are common human pathogens with the potential to cause severe disease and life-long paralysis and even death. The ability for enterovirus infection and vaccination to generate cross-reactive antibody responses in humans and animal models is not completely understood. Understanding whether cross-reactive antibody responses can be elicited is important for vaccine development strategies to counter existing and emerging enterovirus threats to human health and is part of a broader pandemic preparedness program. This study evaluated the generation of cross-reactive enterovirus antibodies in animals after vaccination with inactivated poliovirus vaccine or enterovirus virus-like-particles to inform vaccine development for emerging and re-emerging enteroviruses.