Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes: safety, immunogenicity, and feasibility in Guinea-Bissau

AIDS Res Hum Retroviruses. 2013 Nov;29(11):1504-12. doi: 10.1089/AID.2013.0076. Epub 2013 Jun 21.

Abstract

We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against HIV-1 using IFN-γ ELISpot in this chronically infected African population.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / adverse effects*
  • AIDS Vaccines / immunology
  • AIDS Vaccines / therapeutic use*
  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Antigens, Viral / immunology
  • Antigens, Viral / therapeutic use*
  • CD4 Lymphocyte Count
  • Enzyme-Linked Immunospot Assay
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / therapeutic use
  • Female
  • Guinea-Bissau
  • HIV Infections / therapy*
  • HIV-1 / immunology*
  • Humans
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods*
  • Interferon-gamma / metabolism
  • Liposomes / administration & dosage
  • Male
  • Middle Aged
  • Phosphoproteins / immunology
  • Viral Load
  • Young Adult

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • La protein, human
  • Liposomes
  • Phosphoproteins
  • Interferon-gamma