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

• DOI: 10.1086/314895
• Publication Date: 2002-07-26T14:58:45Z
• Authors: Thomas G. Evans; Michael C. Keefer; Kent J. Weinhold; Mark Wolff; David Montefiori; Geoffrey J. Gorse; Barney S. Graham; M. Juliana McElrath; Mary Lou Clements...; Mark J. Mulligan; Patricia Fast; Mary Clare Walker; Jean‐Louis Excler; Ann‐Marie Duliege; James Tartaglia
• Keywords: AIDS Vaccines; 0301 basic medicine; Vaccines, Synthetic; Genes, Viral; Genetic Vectors; Retroviridae Proteins; HIV Antibodies; HIV Envelope Protein gp120; Lymphocyte Activation; Avipoxvirus; 3. Good health; 03 medical and health sciences; Double-Blind Method; HIV Seronegativity; HIV-1; Humans; Immunization Schedule; T-Lymphocytes, Cytotoxic

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.