Efficacy evaluation of a bivalent subunit vaccine against epidemic PEDV heterologous strains with low cross-protection

(PEDV), which causes diarrhea and high mortality in piglets, has become a major pathogen, and co-epidemics of different subtypes of the virus have become a very thorny problem for the clinical prevention and control of PEDV. However, cross-protection between epidemic G2a and G2b subtype strains has not been observed, and there is currently no vaccine against both G2a and G2b strains. In this study, we demonstrate the low cross-protection between G2a and G2b strains with piglet immunization and challenge tests. The trimeric full-length S proteins of G2a and G2b variants were purified and a bivalent subunit vaccine against PEDV G2a/G2b-S was developed. In active and passive immune protection tests, the bivalent subunit vaccine produced high neutralizing antibody titers and S-specific immunoglobulin G (IgG) and IgA titers against both the G2a and G2b strains in piglets and sows. In the attack phase of the viruses, the clinical symptoms and microscopic lesions in the immunized groups were significantly alleviated. Importantly, the PEDV G2a/G2b-S bivalent subunit vaccine conferred effective passive immunity against PEDV G2a and G2b challenges in the form of colostrum-derived antibodies from the immunized sows. In conclusion, our data demonstrate the low cross-protection of PEDV epidemic G2a and G2b strains and show that the G2a/G2b-S bivalent subunit vaccine is protective against both G2a and G2b strains. It is therefore a candidate vaccine for PEDV prevention. IMPORTANCE: The detection rate of PEDV G2a subtype strains is currently increasing. Although commercial vaccines are available, most vaccines do not exert an ideal protective effect against these strains. Furthermore, there is no definitive research into the cross-protection between G2a and G2b strains, and no bivalent vaccine provides joint protection against both. Therefore, in this study, we investigated the cross-protection between PEDV G2a and G2b strains and designed a candidate bivalent subunit vaccine combining the trimeric S proteins of the G2a and G2b subtypes. We demonstrate that the cross-protection between strains G2a and G2b is poor and that this bivalent subunit vaccine protects piglets from viral attack by inducing both active and passive immunity. This study emphasizes the effectiveness of the PEDV G2a/G2b-S bivalent subunit vaccine and provides a feasible method for the development of efficient PEDV vaccines.