Protection of neonatal mice from lethal enterovirus 71 infection by maternal immunization with attenuated Salmonella enterica serovar Typhimurium expressing VP1 of enterovirus 71

This study describes the potential use of attenuated Salmonella enterica serovar Typhimurium strains to express and deliver VP1 of enterovirus 71 (EV71) as a vaccination strategy to prevent EV71 infection in mice. When orally administered to BALB/c mice, both attenuated carrier strains, CNP101 and SL7207, were able to efficiently invade livers and spleens, while only the virulence plasmid-carrying strain SL7207 persisted for more than 30 days in these organs. A recombinant in vivo-regulated promoter expression plasmid expressing VP1 antigen of EV71 was constructed. The expression of the VP1, directed by the pagC promoter, in attenuated Salmonella was confirmed by Western blot hybridization. Both humoral and cellular immune responses were elicited in mice by oral immunization with such Salmonella-based VP1 vaccines. We evaluated the protective efficacy of the vaccines in mice using a maternal immunization protocol. With a lethal challenge, ICR newborn mice born to dams immunized with Salmonella-based VP1 vaccine showed a 50-60% survival; in contrast, none of the mice in the control group survived the challenge. Our data indicated that Salmonella-based VP1 subunit vaccines are a promising vaccine strategy in the prevention of EV71 infection.