Background:  Most HIV infections occur via mucosal surfaces and CD4 memory cells are the main viral target in these tissues. An important goal of preventive HIV vaccination may be the induction of virus-specific immune responses at mucosal sites to contain locally viral infection and prevent the loss of the T-cell memory population.

Methods:  We compared the efficacy of an intranasally or intramuscularly administered simian immunodeficiency virus (SIV) DNA-modified vaccinia virus Ankara (rMVA) vaccine in delaying loss of memory CD4⁺ T cells and the occurrence of AIDS in SIV_mac251 intrarectally-challenged rhesus macaques. Rectal IgA, systemic IgG, and neutralizing antibody levels, as well as the kinetics of the SIV-specific immune responses, measured as interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) production in stimulated CD4⁺ and CD8⁺ T cells, were assessed before and after challenge. The preservation of the CD4⁺ and CD8⁺ memory T-cell populations was assessed over time after SIV infection. Viral loads and occurrence of AIDS were also evaluated.

Results:  The intranasal vaccination induced higher levels of SIV-specific IgA than the intramuscular immunization but the systemic IgG responses were more significant in the intramuscular group. There were no major differences in the magnitude of the systemic T-cells responses between the vaccinated groups, although the intranasal immunization induced more consistent SIV-specific T-cell responses in the rectal mucosa. Upon challenge, all groups presented similar levels of systemic SIV-specific humoral and cell-mediated responses. A better control of viremia and a more prolonged survival after infection observed in both vaccinated group were associated with the preservation of the CD4⁺ memory T-cell population during the early chronic infection. However, a better preservation of the CD4⁺ memory T-cell population both systemically and in the rectal mucosa and better survival rates were observed over time in the intranasally vaccinated group than in the intramuscularly vaccinated group.

Conclusions: The intranasal or intramuscular SIV vaccinations described here do not protect from SIV infection, but provide significant disease delay than controls. The intranasal immunization appears to provide a significantly better protection from disease when compared to the intramuscular protection. The longer disease-free interval in this group correlates with a more prolonged preservation of the CD4⁺ memory T-cell population that may depend on better viremia control in the gastrointestinal tract.