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

Despite advances in the clinical management of HIV infection, using combina tions 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, How ever, only a few of these strategies, beside those relying on live-attenuat ed 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 inj ection 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 periphera l blood and draining lymph node. Furthermore, these CTLs mere directed agai nst multiple HIV-1 p55(gag) epitopes. This indicated that immunization with p55(gag) VLP primes strong MHC class I-restricted, CD8(+) cell-mediated im mune responses and suggested that HIV-1 p55(gag) VLPs should be a reasonabl e vaccine candidate, when combined with strategies priming cross-neutralizi ng antibodies.