Priming of Strong,Broad,and Long-Lived HIV Type 1 p55 gag -Specific CD8 + Cytotoxic T Cells after Administration of a Virus-Like Particle Vaccine in Rhesus Macaques

Abstract

Despite advances in the clinical management of HIV infection, using combinations of antiretroviral pharmaceuticals, a safe and efficacious vaccine is needed to limit the AIDS pandemic. It is now thought that an effective HIV-1 vaccine should prime both cross-neutralizing antibodies and long-lasting cytotoxic CD8⁺ T lymphocytes (CTLs) recognizing multiple codominant HIV-1 epitopes. To that end, many novel vaccine strategies have been tested. However, only a few of these strategies, beside those relying on live-attenuated viruses, are able to prime strong CTL responses in nonhuman primates and humans. In this study, three rhesus macaques were immunized with HIV-1 p55^gag virus-like particles (VLPs) in the absence of adjuvant to assess the potential of such a vaccine to prime CTL responses. After intramuscular injection of p55^gag VLP, all three animals mounted CTL responses against HIV-1 p55^gag. Notably, these CTLs primed by vaccination recognized naturally processed peptides and were long lived (>8.5 months) both in the peripheral blood and draining lymph node. Furthermore, these CTLs were directed against multiple HIV-1 p55 gag epitopes. This indicated that immunization with p55^gag VLP primes strong M HC class I-restricted, CD8⁺ cell-mediated immune responses and suggested that HIV-1 p55^gag VLPs should be a reasonable vaccine candidate, when combined with strategies priming cross-neutralizing antibodies.