Role of preimmunization virus sequences in cellular immunity in HIV-infected patients during HIV type 1 MN recombinant gp160 immunization

AIDS Res Hum Retroviruses. 1998 Dec 20;14(18):1669-78. doi: 10.1089/aid.1998.14.1669.

Abstract

The effect of patient preimmunization virus sequences on CTL responses during gp160 immunization were studied. Ten HLA-A2+, HIV+ asymptomatic patients with CD4+ T cells >500/mm3 were given two courses of HIV-1 MN rgp160 vaccine over a 2-year period. Envelope epitope-specific CTL responses, using PBMCs, were measured against peptide-coated autologous B lymphoblastoid cell lines. Optimum CTL epitopes were determined by HLA-A2-binding affinity of 9- to 10-mer peptides containing the HLA-A2.1-binding motif. Ten of the high- or intermediate-binding peptides were conserved among >50% of reported clade B HIV strains. These peptide-specific CTL activities and the patient virus sequences in peptide-coding regions were monitored. Six patients showed envelope peptide-specific CTL responses, which correlated with the presence of whole envelope antigen-specific CTL responses. Five of these patients, who showed responses to epitopes in the gp41 region (aa 814-824), had preimmunization virus similar to the vaccine sequence in this region. Three patients who did not show these epitope-specific responses had initially different sequences in the HIV gene encoding that region. The epitope-specific CTL responses appear to reflect recall responses, as only patients infected with virus containing the vaccine sequence developed them and they could be recalled with a second set of vaccine injections. This appears to be reminiscent of the concept of T cell "original antigenic sin." This vaccine was also immunogenic as measured by gp160-specific lymphocyte-proliferative responses. However, increased immune responses did not impact the HIV load or CTL epitope sequences during therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Amino Acid Sequence
  • Cell Cycle
  • Epitopes / chemistry
  • Epitopes / immunology
  • HIV Infections / immunology*
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • Humans
  • RNA, Viral / genetics
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, Synthetic / immunology*
  • Viral Load

Substances

  • AIDS Vaccines
  • Epitopes
  • RNA, Viral
  • Vaccines, Synthetic