Enhanced immunity to human immunodeficiency virus (HIV) envelope elicited by a combined vaccine regimen consisting of priming with a vaccinia recombinant expressing HIV envelope and boosting with gp160 protein

Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1882-6. doi: 10.1073/pnas.90.5.1882.

Abstract

Transmission studies have suggested that an optimal human immunodeficiency virus type 1 (HIV-1) vaccine should induce both neutralizing antibodies and cytolytic T cells to eliminate free virus and infected cells. A phase I trial in healthy HIV-1-seronegative persons was conducted with a combination HIV-1 vaccine regimen (strain IIIB) consisting of priming with a recombinant vaccinia (vac/env) virus expressing HIV-1 envelope and boosting with a gp160 glycoprotein derived from a recombinant baculovirus (rgp160). T-cell and antibody responses detected after immunization with either vac/env alone or rgp160 alone were generally of low magnitude and transient, and no subject developed neutralizing antibodies. In contrast, recipients of the combination regimen demonstrated in vitro T-cell proliferative responses to homologous HIV-1 antigens that were 3- to 10-fold higher than responses with either vaccine alone, and these responses were sustained for > 18 months in 75% of recipients. Moreover, both CD8+ and CD4+ cytolytic T cells were detected. Antibody responses (titer, 1:800 to 1:102,400) to homologous HIV envelope developed in all recipients of the combination regimen, and neutralizing antibodies were detected in 7 of 13. Thus, immunization with a live virus vaccine followed by boosting with a soluble protein offers promise for inducing the broad immunity needed in an HIV vaccine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Baculoviridae
  • Cytotoxicity, Immunologic
  • Gene Products, env / chemistry
  • Gene Products, env / immunology*
  • HIV Antigens / immunology*
  • HIV Envelope Protein gp160
  • HIV-1 / immunology*
  • Humans
  • Lymphocyte Activation
  • Protein Precursors / chemistry
  • Protein Precursors / immunology*
  • Solubility
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Synthetic
  • Vaccinia virus
  • Viral Envelope Proteins / immunology

Substances

  • Gene Products, env
  • HIV Antigens
  • HIV Envelope Protein gp160
  • Protein Precursors
  • Vaccines, Synthetic
  • Viral Envelope Proteins