An attenuated EIAV vaccine strain induces significantly different immune responses from its pathogenic parental strain although with similar in vivo replication pattern

The EIAV (equine infectious anemia virus) multi-species attenuated vaccine EIAVDLV121 successfully prevented the spread of equine infectious anemia (EIA) in China in the 1970s and provided an excellent model for the study of protective immunity to lentiviruses. In this study, we compared immune responses induced by EIAVDLV121 to immunity elicited by the virulent EIAVLN40 strain and correlated immune responses to protection from infection. Horses were randomly grouped and inoculated with either EIAVDLV121 (Vaccinees, Vac) or a sublethal dose of EIAVLN40 (asymptomatic carriers, Car). Car horses became EIAVLN40 carriers without disease symptoms. Two of the four Vac horses were protected against infection and the other two had delayed onset or reduced severity of EIA with a lethal EIAVLN40 challenge 5.5 months post initial inoculation. In contrast, all three Car animals developed acute EIA and two succumbed to death. Specific humoral and cellular immune responses in both Vac and Car groups were evaluated for potential correlations with protection. These analyses revealed that although plasma viral loads remained between 103 and 105 copies/ml for both groups before EIAVLN40 challenge, Vac-treated animals developed significantly higher levels of conformational dependent, Env-specific antibody, neutralizing antibody as well as significantly elevated CD4+ T cell proliferation and IFN-γ-secreting CD8+ T cells than those observed in EIAVLN40 asymptomatic carriers. Further analysis of protected and unprotected cases in vaccinated horses identified that cellular response parameters and the reciprocal anti-p26-specific antibody titers closely correlated with protection against infection with the pathogenic EIAVLN40. These data provide a better understanding of protective immunity to lentiviruses.

► We compared immune responses elicited by a vaccine EIAVDLV121 or virulent EIAVLN40 strain.
► Infection of EIAVDLV121 and sublethal dose of EIAVLN40 resulted in similar plasma viral loads.
► EIAVDLV121 stimulated significantly higher level of conformational dependent env and neutralizing antibodies.
► EIAVDLV121 significantly enhanced CD4+ T cell responses especially in the early stage.
► p26 Capsid-specific antibody appeared to be a marker of protective immunity to EIAV.