Lipopeptides induce cell-mediated anti-HIV immune responses in seronegative volunteers.
OBJECTIVE
Test the efficacy of a mixture of six NEF (N1, N2, N3), GAG (G1, G2) and ENV (E) lipopeptides in the induction of B- and T-cell anti-HIV responses.


METHODS
A randomized phase I open-label dose-finding trial. Twenty-eight healthy seronegative volunteers received the lipopeptides, with or without the adjuvant QS21.


METHODS
Anti-HIV-peptide antibodies were detected by enzyme-linked immunosorbent assay and Western blotting. Induction of cellulary responses was assessed by proliferative test and (51)Cr-release assay.


RESULTS
Local and systemic adverse reactions were always mild or moderate. After three injections an antibody response was detected in 25 out of 28 volunteers (89%). T cells from 19 (79%) of the 24 volunteers proliferated in response to at least one peptide. The majority of the volunteers had induced a multispecific proliferative response; that is, cells from volunteers proliferated to two (five of 19), three (five of 19), four (three of 19) or five peptides (one of 19). Cytotoxic responses by anti-HIV CD8+ lymphocytes could be tested in 24 volunteers, 13 (54%) of whom had clear and reproducible responses, with strong activity in the remaining 12 (> 20% of specific lysis), and polyepitopic responses were detected in at least seven of the 13 responders. Cytotoxic responses were found against the whole NEF protein (clade B LAI) in three of four tested volunteers and cross-reactions with the proteins of clade B (MN) and clade A (Bangui) HIV-1 strains, and also HIV-2 ROD, were detected in one of two tested volunteers.


CONCLUSIONS
Lipopeptides are promising immunogens for an AIDS vaccine.
Pialoux
G
G
Hopital Rothschild, Paris, France. gilles.pialoux@rth.ap-hop-paris.fr
Gahéry-Ségard
H
H
Sermet
S
S
Poncelet
H
H
Fournier
S
S
Gérard
L
L
Tartar
A
A
Gras-Masse
H
H
Levy
J P
JP
Guillet
J G
JG
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000328:Adult; D000595:Amino Acid Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015693:Gene Products, nef / Q000737:chemistry*; D015483:HIV Antibodies / Q000097:blood; D018023:HIV Seronegativity / Q000276:immunology*; D006801:Humans; D008074:Lipoproteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016915:AIDS Vaccines; D015693:Gene Products, nef; D015483:HIV Antibodies; D008074:Lipoproteins; D010446:Peptide Fragments