Multiepitopic B- and T-cell responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine.
We have attempted to develop an anti-human immunodeficiency virus (HIV) lipopeptide vaccine with several HIV-specific long peptides modified by C-terminal addition of a single palmitoyl chain. A mixture of six lipopeptides derived from regulatory or structural HIV-1 proteins (Nef, Gag, and Env) was prepared. A phase I study was conducted to evaluate immunogenicity and tolerance in lipopeptide vaccination of HIV-1-seronegative volunteers given three injections of either 100, 250, or 500 microg of each lipopeptide, with or without immunoadjuvant (QS21). This report analyzes in detail B- and T-cell responses induced by vaccination. The lipopeptide vaccine elicited strong and multiepitopic B- and T-cell responses. Vaccinated subjects produced specific immunoglobulin G antibodies that recognized the Nef and Gag proteins. After the third injection, helper CD4(+)-T-cell responses as well as specific cytotoxic CD8(+) T cells were also obtained. These CD8(+) T cells were able to recognize naturally processed viral proteins. Finally, specific gamma interferon-secreting CD8(+) T cells were also detected ex vivo.
Gahéry-Ségard
H
H
Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM Unit¿e 445, Institut Cochin de G¿en¿etique Mol¿eculaire, Universit¿e Ren¿ee Descartes, H¿opital Cochin, 75014 Paris, France. gahery@icgm.cochin.inserm.fr
Pialoux
G
G
Charmeteau
B
B
Sermet
S
S
Poncelet
H
H
Raux
M
M
Tartar
A
A
Lévy
J P
JP
Gras-Masse
H
H
Guillet
J G
JG
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003257:Consumer Product Safety; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015693:Gene Products, nef; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D008074:Lipoproteins; D010446:Peptide Fragments; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma