Evaluation of a lipopeptide immunogen as a therapeutic in HIV type 1-seropositive individuals. Academic Article uri icon

Overview

MeSH

  • Adult
  • Amino Acid Sequence
  • Cytotoxicity Tests, Immunologic
  • Epitopes, T-Lymphocyte
  • Humans
  • Male
  • Molecular Sequence Data
  • Peptides
  • Pilot Projects
  • T-Lymphocytes, Cytotoxic
  • Vaccination
  • Viral Load

MeSH Major

  • AIDS Vaccines
  • Gene Products, gag
  • HIV Infections
  • HIV-1
  • Lipoproteins

abstract

  • 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.

publication date

  • March 1, 2000

has subject area

  • AIDS Vaccines
  • Adult
  • Amino Acid Sequence
  • Cytotoxicity Tests, Immunologic
  • Epitopes, T-Lymphocyte
  • Gene Products, gag
  • HIV Infections
  • HIV-1
  • Humans
  • Lipoproteins
  • Male
  • Molecular Sequence Data
  • Peptides
  • Pilot Projects
  • T-Lymphocytes, Cytotoxic
  • Vaccination
  • Viral Load

Research

keywords

  • Clinical Trial
  • Controlled Clinical Trial
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/088922200309214

PubMed ID

  • 10716371

Additional Document Info

start page

  • 337

end page

  • 343

volume

  • 16

number

  • 4