Priming of strong, broad, and long-lived HIV type 1 p55gag-specific CD8+ cytotoxic T cells after administration of a virus-like particle vaccine in rhesus macaques

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 mere directed against multiple HIV-1 p55(gag) epitopes. This indicated that immunization with p55(gag) VLP primes strong MHC 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.