New CD4+ and CD8+ T cell responses induced in chronically HIV type-1-infected patients after immunizations with an HIV type 1 lipopeptide vaccine.
We showed that an anti-HIV lipopeptide vaccine injected to HIV-uninfected volunteers was well tolerated and able to induce a specific CD4(+) and CD8(+) T cell responses. The same vaccine was injected in HIV-1 chronically infected patients controlled by HAART to evaluate its immunogenicity. In this trial, 24 patients were immunized three times with a mixture of six lipopeptides (Nef 66-97, Nef 117-147, Nef 182-205, Gag 183-214, Gag 253-284, and Env 303-335) at 0, 3, and 6 weeks. We studied the HIV-1-specific CD4(+) T cell proliferative responses. The IFN-gamma secretion by activated CD8(+) T cells was evaluated, using an ex vivo ELISpot assay and 60 CD8(+) T cell epitopes derived from the vaccine. Before immunization (W0), anti-HIV CD4(+) T cell responses to Gag, Nef, and Env large peptides were detected in 7/23 (30%) analyzable patients. After three injections, 17/23 (74%) patients had a proliferative response and 16 of them induced new specific CD4(+) T cell responses. At W0, CD8(+) T cell responses to HIV-1 epitopes were detected in 6/23 (26%) patients. After vaccination, 16/23 (70%) patients showed CD8(+) T cell responses and 13 of these patients induced new T cell responses to 25 different HIV-1 epitopes. These HIV-1 epitopes were detected in patients with various HLA class I molecules (HLA-A2, -A3/A11, -A24, -B7 superfamily, -B8), as found in the majority of the white population. Lipopeptides induce new anti-HIV T cell responses in vaccinated infected patients and could be used as a new immunotherapy strategy. The majority of these responders induced specific new CD4(+) and CD8(+) T cell responses.
Gahery
Hanne
H
Institut Cochin, Département d'Immunologie, INSERM U567, CNRS UMR8104, Université René Descartes, 75014 Paris, France. gahery@cochin.inserm.fr
Daniel
Nathalie
N
Charmeteau
Bénédicte
B
Ourth
Lucie
L
Jackson
Angéla
A
Andrieu
Muriel
M
Choppin
Jeannine
J
Salmon
Dominique
D
Pialoux
Gilles
G
Guillet
Jean-Gerard
JG
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D055666:Lipopeptides; D008074:Lipoproteins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; C512627:HIV type 1 lipopeptide vaccine; D055666:Lipopeptides; D008074:Lipoproteins; D018074:Vaccines, Conjugate; D022223:Vaccines, Subunit; D054311:nef Gene Products, Human Immunodeficiency Virus