Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen. AIDS Vaccine Evaluation Group.

Publication Type
Journal Article
Year of Publication
1998
Authors
Corey, L; McElrath, M J; Weinhold, K; Matthews, T; Stablein, D; Graham, B; Keefer, M; Schwartz, D; Gorse, G
Secondary
J Infect Dis
Volume
177
Pagination
301-9
Date Published
1998 Feb
Keywords
Adolescent; Adult; AIDS Vaccines; Antibodies, Blocking; Antibodies, Viral; Antibody Affinity; CD4 Antigens; CD8-Positive T-Lymphocytes; Cytotoxicity Tests, Immunologic; Double-Blind Method; Female; HIV Antibodies; HIV Antigens; HIV Envelope Protein gp120; HIV Envelope Protein gp160; HIV Infections; HIV-1; Humans; Male; Middle Aged; Neutralization Tests; Recombinant Proteins; T-Lymphocytes, Cytotoxic; Vaccines, Combined; Vaccines, Synthetic; Vaccinia virus
Abstract

Effective human immunodeficiency virus (HIV) vaccination may require induction of neutralizing antibodies (NAs) and CD8+ cytotoxic T lymphocytes (CTL) to prevent transmission and control early infection. Recombinant envelope proteins induce NAs but rarely CD8+ CTL responses, and vaccinia vectors containing HIV-1 envelope elicit CD8+ cytotoxicity but few NAs. To benefit from both approaches, 56 vaccinia-naive subjects were randomized to a regimen of priming with recombinant vaccinia gp160LAI and boosting with recombinant gp120SF-2, gp120LAI, gp120MN, or gp160MN. Of 51 persons for whom assays were done, 26 demonstrated envelope-specific CTL. Boosting with gp120, compared with gp160, elicited significantly more NAs and CD4-blocking antibodies. Neutralization of the homologous and heterologous HIV-1 laboratory strains occurred in all subjects receiving vac/env and gp120 and was detectable in 91% of the subjects for >6 months. Thus, vaccine regimens in which one component elicits primarily CTL and the other NAs offer promise for the development of an effective HIV-1 vaccine strategy.