We studied cytotoxic T lymphocyte (CTL) cross-reactivity between human immunodeficiency virus type 1 (HIV-1) subtypes within a group of infants infected with either HIV-1 B or non-B clade. Fifteen children were infected with a clade B virus. Nine were infected with non-B virus, including two clade A, four clade D, two clade F, and one clade G. CTL activities from in vitro activated peripheral blood mononuclear cells were tested against autologous cell line infected with recombinant vaccinia viruses encoding for Env, Gag, Pol, or Nef proteins from a clade A or B isolate. HIV-1-specific CTL elicited from infection with clade B virus could lyse targets expressing clade A proteins, and vice versa. In infants with positive CTL responses, cross-clade recognition was predominant and was detected within 88% of the Pol, 83% of the Nef, 67% of the Gag, and 55% of the Env responders. Longitudinal studies showed that CTL cross-reactivity to both B and A targets was stable for several years. Elicitation of CTL reactivities capable of elimination of virus-infected cells is an important goal for the development of an efficient AIDS vaccine. The significant cross-reactivity of CTL shown in this study supports the concept that vaccines developed using a single-clade immunogen may be applicable to induce broadly reactive T cell responses.

A vaccine against human immunodeficiency virus (HIV) should induce virus-specific cytotoxic T lymphocyte (CTL) activity. Immunization of uninfected volunteers with a canarypox virus expressing HIV envelope was carried out in a phase I trial. Two injections of canarypox expressing HIV-1MN gp 160 (months 0 and 1) were followed by two boosts of recombinant envelope protein (months 3 and 6). HIV envelope-specific CTL were detected in peripheral blood mononuclear cells stimulated with autologous HIV-1-infected blast cells. T cell lines were obtained from 18 of 20 donors: CTL were detected at least once following immunization in 7 (39%) of these 18. This activity was mediated by major histocompatibility complex class I-restricted CD3+CD8+ T cells. For two subjects, this activity was still present 2 years after the initial immunization. The CTL responses with this prime-boost regimen are the best observed with any HIV vaccine tested in humans.

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SUMMARYThe HIV gag polyprotein is a major target for recognition by CTL in infected humans. Using recombinant vaccinia viruses (rW) expressing truncations of the p24gag, and the p18gag, pl5gag and HIV-2 p565ag proteins, the characterization of epitope regions recognized by in vitrostimulated peripheral blood mononuclear cells (PBMC) from 18 infected patients has been studied. The gag-specific response of most individuals is polyclonal and multispecific, and interindividual variations between target epitope regions were frequently observed, despite shared MHC alleles. As CTL may play an important role in the control of HIV replication in infected hosts, these results have important implications for designing vaccine strategies.