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

The effect of patient preimmunization virus sequences on CTL responses duri ng gp160 immunization were studied. Ten HLA-A2(+), HIV+ asymptomatic patien ts with CD4(+) T cells >500/mm(3) were given two courses of HIV-1 MN rgp160 vaccine over a 2-year period. Envelope epitope-specific CTL responses, usi ng 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 report ed clade B HIV strains. These peptide-specific CTL activities and the patie nt virus sequences in peptide-coding regions were monitored. Six patients s howed envelope peptide-specific CTL responses, which correlated with the pr esence of whole envelope antigen-specific CTL responses. Five of these pati ents, who showed responses to epitopes in the gp41 region (aa 814-824), had preimmunization virus similar to the vaccine sequence in this region. Thre e patients who did not show these epitope-specific responses had initially different sequences in the HIV gene encoding that region. The epitope-speci fic CTL responses appear to reflect recall responses, as only patients infe cted with virus containing the vaccine sequence developed them and they cou ld 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-proliferativ e responses. However, increased immune responses did not impact the HIV loa d or CTL epitope sequences during therapy.