Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV.

An effective vaccine against sexual transmission of human immunodeficiency virus (HIV) should elicit both systemic and mucosal immune responses. In this study, to examine the possibility of using an attenuated virus for mucosal immunization, four female macaques were intranasally or intravenously administered with a chimeric simian-human immunodeficiency virus with a deleted nef gene (SHIV-dn). Although all the monkeys had anti-HIV-1 antibodies with neutralizing activity in the plasma, the intranasally immunized monkeys had much higher levels of HIV-1 Env-specific IgG and IgA antibodies in mucosal secretions compared with the intravenously immunized monkeys. Moreover, three of four intranasally immunized monkeys were completely protected from intravaginal challenge with a pathogenic virus, SHIV-89.6P, whereas only one intravenously immunized monkey was protected. Thus, intranasal immunization of an attenuated virus can induce the protective efficacy against intravaginal infection.