A Canarypox Vaccine Expressing Multiple Human Immunodeficiency Virus Type 1 Genes Given Alone or with Rgp120 Elicits Broad and Durable CD8+ Cytotoxic T Lymphocyte Responses in Seronegative Volunteers

Publication Type
Journal Article
Year of Publication
1999
Authors
Evans, TG; Keefer, MC; Weinhold, KJ; Wolff, M; Montefiori, D; Gorse, GJ; Graham, BS; McElrath, MJ; Clements-Mann, ML; Mulligan, MJ; Fast, P; Walker, MC; Excler, JL; Duliege, AM; Tartaglia, J; the NIAID AIDS Vaccine Evaluation Group
Secondary
J Infec Dis
Volume
180
Start Page
290
Pagination
290-298
Date Published
08/1999
Keywords
AIDS Vaccines; ALVAC-HIV vCP300; Avipoxvirus; Genetic Vectors; HIV Antibodies; HIV Envelope Protein gp120; HIV Seronegativity; HIV-1; Immunization Schedule; Lymphocyte Activation; Retroviridae Proteins; T-Lymphocytes- Cytotoxic; Vaccines- Synthetic
Abstract
Induction of CD8+ cytotoxic T cells is considered one of the important correlates for the protective efficacy of candidate human immunodeficiency virus type 1 (HIV-1) vaccines. To induce CD8+ cytotoxic T lymphocytes (CTLs) along with neutralizing antibody and CD4+ T cell help, a live canarypox virus construct expressing gp120, transmembrane gp41, the gag and protease genes, and sequences containing CTL epitopes in nef and pol was given simultaneously with, or followed by, rgp120 SF2. CD8+ CTLs were detected in 61% of volunteers at some time during the trial. Three to 6 months after the last immunization, the gene-specific responses were gag, 26/81; env, 17/77; nef, 12/77; and pol, 3/16. Simultaneous immunization with the canarypox vector and the subunit, beginning with the initial immunization, resulted in earlier antibody responses. In summary, a strategy of immunization with a canarypox vector expressing multiple genes of HIV-1 given with gp120 results in durable CD8+ CTL responses to a broad range of epitopes.