Protection against establishment of retroviral persistence by vaccination with a live attenuated virus

Many human viruses not only cause acute diseases but also establish persist ent infections. Such persistent viruses can cause chronic diseases or can r eactivate to cause acute diseases in AIDS patients or patients receiving im munosuppressive therapies. While the prevention of persistent infections is an important consideration in the design of modern vaccines, surprisingly little is known about this aspect of protection. In the current study, we t ested the feasibility of vaccine prevention of retroviral persistence by us ing a Friend virus model that we recently developed. In this model, persist ent virus can be detected at very low levels by immunosuppressing the host to reactivate virus or by transferring persistently infected spleen cells i nto highly susceptible mice, Two vaccines were analyzed, a recombinant vacc inia virus vector expressing Friend virus envelope protein and a live atten uated Friend virus. Both vaccines reduced pathogenic virus loads to levels undetectable by infectious center assays, However, only the live, attenuate d vaccine prevented immunosuppression-induced reactivation of persistent vi rus. Thus, even very low levels of persistent Friend virus posed a signific ant threat during immunosuppression, Our results demonstrate that vaccine p rotection against establishment of retroviral persistence is attainable.