The lymphocyte composition highly varies between different mucosal sites, and data obtained from biopsy and necropsy samples were mostly not comparable.
We investigated the immunogenicity and efficacy of a bimodal prime/boost vaccine regimen given by various routes in the Simian immunodeficiency virus (SIV) rhesus monkey model for AIDS. Twelve animals were immunized with SIV DNA-vectors followed by the application of a recombinant adenovirus (rAd5) expressing the same genes either intramuscularly (i.m.) or by oropharyngeal spray. The second rAd5-application was given i.m. All vaccinees plus six controls were challenged orally with SIVmac239 12 weeks post-final immunization. Both immunization strategies induced strong SIV Gag-specific IFN-gamma and T-cell proliferation responses and mediated a conservation of CD4(+) memory T-cells and a reduction of viral load during peak viremia following infection. Interestingly, the mucosal group was superior to the systemic group regarding breadth and strength of SIV-specific T-cell responses and exhibited lower vector specific immune responses. Therefore, our data warrant the inclusion of mucosal vector application in a vaccination regimen which makes it less invasive and easier to apply.
The availability of an effective vaginal microbicide would be a major step toward containment of HIV transmission as well as allowing women self-protection against HIV infection. Here we evaluated the efficacy of vaginal application of the potent nonnucleoside reverse transcriptase inhibitor (NNRTI) MC 1220 against vaginal challenge of macaques with RT-SHIV, a chimeric simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT) gene of HIV-1. Challenge infection of monkeys with RT-SHIV currently represents the only nonhuman primate model available to test the anti-HIV-1 effects of NNRTIs. Two different gel formulations containing different MC 1220 concentrations were evaluated for efficacy in female rhesus macaques exposed to RT-SHIV. Five groups of five animals each were treated with two different gel compositions containing no drug, 0.1% or 0.5% MC 1220, followed by vaginal RT-SHIV challenge 30 min later. One animal in each group treated with the low concentration of MC 1220 as well as one control animal remained uninfected after vaginal challenge. By contrast, three of the animals receiving 0.5% MC 1220 remained uninfected, suggesting a threshold of the drug. Despite being negative for plasma viral RNA and absence of seroconversion, almost all uninfected animals exhibited SIV-specific T cells, either in the periphery or in lymph nodes draining the portal of virus entry. Our results make MC 1220 a promising compound for further development as a topical microbicide and warrant additional testing with improved formulation, long-lasting vaginal delivery systems, or even combinations with other inhibitors.
Our study gives an extended overview of cross-reactive antibodies for flow cytometric analysis of immune cells as well as baseline values for different immune parameters in healthy common marmosets.
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