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.
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.
Cooney
E L
EL
Department of Medicine, University of Washington, Seattle 98195.
McElrath
M J
MJ
Corey
L
L
Hu
S L
SL
Collier
A C
AC
Arditti
D
D
Hoffman
M
M
Coombs
R W
RW
Smith
G E
GE
Greenberg
P D
PD
D016367:Baculoviridae; D003602:Cytotoxicity, Immunologic; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic; D014616:Vaccinia virus; D014759:Viral Envelope Proteins / Q000276:immunology
D015686:Gene Products, env; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins