Evaluation of a lipopeptide immunogen as a therapeutic in HIV type 1-seropositive individuals.
A 32-amino acid HIV-1 Gag immunogen was assessed for its ability to augment existing virus-specific CTL responses in chronically HIV-1-infected individuals. The immunogen was an HIV-1 synthetic lipopeptide conjugate composed of an N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R)-propyl-N-(R)-cysteinyl] group covalently coupled to a synthetic 32-amino acid Gag peptide containing at least 5 CTL epitopes known to be restricted by HLA-A33, -B8, -B27, -B35, and -Bw62. This potential immunotherapeutic was first determined to be safe in six HIV-1-seropositive subjects, with no adverse clinical effects noted during a 182-day period after administration of a dose of 350 microg. The immunogenicity of this lipopeptide conjugate was then assessed in a pilot study in nine HIV-1-seropositive volunteers with peripheral blood CD4+ lymphocyte counts of >500/microl. Three groups of individuals were studied: HLA-selected subjects who received 350 microg of the immunogen on days 0, 28, and 56 (four subjects); HLA-selected subjects who received a placebo according to a similar inoculation schedule (three subjects); and HLA-mismatched subjects who received the experimental immunogen (two subjects). All subjects were monitored for 26 weeks. After treatment, PBLs from two of the four HLA-selected subjects who received the experimental immunogen showed a transient increase in Gag peptide-specific bulk CTL activity. None of the placebo-vaccinated or vaccinated HLA-mismatched subjects showed any change in bulk Gag peptide-specific CTL activity. However, no consistent decrease in plasma HIV-1 RNA levels was noted in any of the subjects. The present study illustrates that this peptide formulation may not be a sufficiently potent immunogen to significantly augment HIV-1-specific CTLs and to decrease virus load in HIV-1-seropositive individuals.
Seth
A
A
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Yasutomi
Y
Y
Jacoby
H
H
Callery
J C
JC
Kaminsky
S M
SM
Koff
W C
WC
Nixon
D F
DF
Letvin
N L
NL
D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000328:Adult; D000595:Amino Acid Sequence; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D010865:Pilot Projects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019562:Viral Load
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D008074:Lipoproteins; D010455:Peptides