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 p55gag 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 p55gag VLP, all three animals mounted CTL responses against HIV-1 p55gag. 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 p55gag epitopes. This indicated that immunization with p55gag VLP primes strong MHC class I-restricted, CD8+ cell-mediated immune responses and suggested that HIV-1 p55gag VLPs should be a reasonable vaccine candidate, when combined with strategies priming cross-neutralizing antibodies.
Paliard
X
X
Chiron Corporation, Emeryville, CA 94608-2916, USA.
Liu
Y
Y
Wagner
R
R
Wolf
H
H
Baenziger
J
J
Walker
C M
CM
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008253:Macaca mulatta; D010455:Peptides / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination; D014771:Virion / Q000276:immunology
D016915:AIDS Vaccines; D015683:Gene Products, gag; D010455:Peptides; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1