Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope

Abstract

Worldwide, the majority of human immunodeficiency virus (HIV) infections occur by heterosexual transmission. Thus, the development of a vaccine that can prevent intravaginal HIV infection is an important goal of AIDS vaccine research. To determine which single or combination of systemic and mucosal routes of immunizations of female rhesus macaques with an HIV-1 SF162 envelope protein vaccine induced protection against intravaginal challenge with SHIV. Female rhesus macaques were immunized with an HIV-1 SF162 envelope protein vaccine administered systemically (intramuscularly), or mucosally (intranasally), or as a sequential combination of both routes. The macaques were then challenged intravaginally with SHIV SF162P4, expressing an envelope that is closely matched (homologous) to the vaccine. Macaques receiving intramuscular immunizations, alone or in combination with intranasal immunizations, were protected from infection, with no detectable plasma viral RNA, provirus, or seroconversion to nonvaccine viral proteins, and better preservation of intestinal CD4+ T cells. Serum neutralizing antibodies against the challenge virus appeared to correlate with protection. The results of this study demonstrate that, in the nonhuman primate model, it is possible for vaccine-elicited immune responses to prevent infection after intravaginal administration of virus.