Delayed-type hypersensitivity responses to HIV Gag p24 relate to clinical outcome after peptide-based therapeutic immunization for chronic HIV infection

APMIS. 2012 Mar;120(3):204-9. doi: 10.1111/j.1600-0463.2011.02843.x. Epub 2011 Nov 27.

Abstract

Therapeutic immunization in chronic HIV infection aims to induce durable, HIV-specific immune responses capable of controlling disease progression, but immunological correlates of clinical efficacy are poorly defined. We have previously immunized 38 patients with a mixture of four short Gag p24-like conserved peptides (Vacc-4x) targeting skin dendritic cells. Antiretroviral treatment (ART) was initially stopped after completed immunizations and resumed post-protocol during regular clinical follow-up according to current guidelines. Four years after enrolment, Vacc-4x-specific cellular responses were evaluated in vivo by delayed-type hypersensitivity (DTH) skin test, and in vitro by a T-cell proliferation assay. Kaplan-Meier product-limit estimates were used to analyse time until ART was resumed. Peptide-specific cellular immune responses induced by Vacc-4x had persisted 4 years after the last immunization in terms of unchanged DTH independent of ART and detectable proliferative T-cell responses which correlated to the native peptides (R = 0.73, p = 0.01). Circulating bifunctional (IFN-γ and IL-10) Vacc-4x-specific T-cell clones were detected in 43% of patients. Subjects with the strongest post-immunization DTH responses appeared to start ART later compared with DTH low responders (p = 0.07). These data suggest that DTH responses should be further evaluated as a new and convenient tool for predicting clinical efficacy in trials testing therapeutic immunizations.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • AIDS Vaccines / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cohort Studies
  • Follow-Up Studies
  • HIV Core Protein p24 / immunology*
  • HIV Infections / immunology*
  • HIV Infections / therapy*
  • HIV-1 / immunology*
  • Humans
  • Hypersensitivity, Delayed / immunology*
  • Immunity, Cellular / immunology*
  • Immunization / methods
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Kaplan-Meier Estimate
  • Prospective Studies
  • RNA, Viral / blood

Substances

  • AIDS Vaccines
  • HIV Core Protein p24
  • RNA, Viral
  • Vacc-4x
  • Interleukin-10
  • Interferon-gamma