Memory Cytotoxic T Lymphocyte Responses in Human Immunodeficiency Virus Type 1 (HIV-1)-Negative Volunteers Immunized with a Recombinant Canarypox Expressing gp160 of HIV-1 and Boosted with a Recombinant gp160

A vaccine against human immunodeficiency virus (HIV) should induce virus-specific cytotoxic T lymphocyte (CTL) activity. Immunization of uninfected volunteers with a canarypox virus express­ ing HIV envelope was carried out in a phase I trial. Two injections of canarypox expressing HIV­ l M N gp160 (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-l-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. Vaccination against the human immunodeficiency virus type I (HIV-I) is a key strategy for the eventual control of the AIDS pandemic. Since the discovery of the etiologic agent of AIDS, different candidate vaccines have been designed and developed, including whole killed virus, live attenuated virus, virus-like particles including pseudovirions, protein subunits based on HIV structural genes, peptides based on selected im­ munoreactive parts of the viral proteins, live recombinant viral or bacterial vectors, and DNA-based immunogens encoding one or more HIV proteins [1-3]. Live recombinant vaccinia viruses have been used successfully to induce protective immu­ nity against animal infectious diseases such as rabies [4], but because the use ofvaccinia virus for human vaccination against smallpox has been shown to induce rare but serious complica­ tions [5], other recombinant poxviruses such as avian poxvi­ ruses have been developed [6, 7]. As was the case for most live expression vectors in AIDS vaccine studies, initial efforts have focused on products based on the HIV-I envelope protein, since several epitopes of env have been described to induce neutralizing antibodies and cell-mediated immune responses, including cytotoxic T lymphocytes (CTL). In HIV-seronegative volunteers at low risk ofHIV infection, the safety and immuno