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.
Publication types
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Clinical Trial
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Multicenter Study
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Randomized Controlled Trial
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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AIDS Vaccines / immunology
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Adolescent
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Adult
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Antibodies, Blocking / immunology
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Antibodies, Viral / analysis
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Antibodies, Viral / immunology
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Antibody Affinity / immunology
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CD4 Antigens / immunology
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CD8-Positive T-Lymphocytes / immunology*
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Cytotoxicity Tests, Immunologic
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Double-Blind Method
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Female
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HIV Antibodies / analysis
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HIV Antibodies / immunology*
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HIV Antigens / genetics
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HIV Antigens / immunology*
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HIV Envelope Protein gp120 / genetics
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HIV Envelope Protein gp120 / immunology
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HIV Envelope Protein gp160 / genetics
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HIV Envelope Protein gp160 / immunology
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HIV Infections / genetics
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HIV Infections / immunology*
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HIV Infections / prevention & control
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HIV-1 / genetics
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HIV-1 / immunology*
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Humans
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Male
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Middle Aged
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Neutralization Tests
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Recombinant Proteins / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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Vaccines, Combined / immunology
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Vaccines, Synthetic / immunology
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Vaccinia virus / genetics
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Vaccinia virus / immunology
Substances
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AIDS Vaccines
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Antibodies, Blocking
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Antibodies, Viral
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CD4 Antigens
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HIV Antibodies
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HIV Antigens
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HIV Envelope Protein gp120
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HIV Envelope Protein gp160
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Recombinant Proteins
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Vaccines, Combined
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Vaccines, Synthetic