Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection

Clin Immunol. 2013 Feb;146(2):120-30. doi: 10.1016/j.clim.2012.12.005. Epub 2012 Dec 21.

Abstract

We investigated the potential of inducing additional T-cell immunity during chronic HIV-1 infection directed to subdominant HIV-1 epitopes from common HLA-supertypes. Ten treatment-naïve HIV-1-infected individuals were immunized with peptides in the adjuvant CAF01. One individual received placebo. T-cell immunogenicity was examined longitudinally by a flow cytometry (CD107a, IFNγ, TNFα, IL-2 and/or MIP1β expression) as well as IFNγ ELISPOT. Safety was evaluated by clinical follow up combined with monitoring of biochemistry, hematology, CD4 T-cell counts and viral load. New CD4 and CD8 T-cell responses specific for one or more vaccine epitopes were induced in 10/10 vaccinees. The responses were dominated by CD107a and MIP1β expression. There were no significant changes in HIV-1 viral load or CD4 T-cell counts. Our study demonstrates that the peptide/CAF01 vaccine is safe and that it is possible to generate new HIV-1 T-cell responses to defined epitopes in treatment-naïve HIV-1-infected individuals.

Trial registration: ClinicalTrials.gov NCT01009762.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / therapeutic use*
  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / therapeutic use*
  • Female
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • HIV Infections / therapy*
  • HLA-A Antigens / administration & dosage
  • HLA-A Antigens / genetics
  • HLA-B Antigens / administration & dosage
  • HLA-B Antigens / genetics
  • HLA-C Antigens / administration & dosage
  • HLA-C Antigens / genetics
  • Humans
  • Immunodominant Epitopes / administration & dosage
  • Immunodominant Epitopes / immunology
  • Immunodominant Epitopes / therapeutic use*
  • Male
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / immunology
  • Peptides / therapeutic use*
  • Single-Blind Method
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • Immunodominant Epitopes
  • Peptides

Associated data

  • ClinicalTrials.gov/NCT01009762