A vaccinia-gp160-based vaccine but not a gp160 protein vaccine elicits anti-gp160 cytotoxic T lymphocytes in some HIV-1 seronegative vaccinees.
Cytotoxic T lymphocytes (CTL) play an important role in the immune response to viral infection by recognizing and destroying infected cells. HIV-1 elicits an unusually strong CTL response in infected individuals and clearance of the viremia of acute infection coincides with the development of HIV-specific CTL. Because HIV-specific CTL may provide protection against de novo viral infection, we compared the CTL response in seronegative volunteers treated with two vaccination approaches. Seven volunteers were immunized with a live recombinant vaccinia virus expressing the HIV envelope protein gp160LAI (HIVAC-1e) and boosted with 640 micrograms recombinant baculovirus-expressed gp160LAI in alum 1-13 months later. In a second study, three volunteers underwent four successive immunizations with 640 micrograms subunit gp160LAI in alum at 0, 1, 6, and 12 months. The first vaccination strategy using a liver vector would be expected to generate gp160-specific CTL, while for the second, using only whole-protein subunit, the generation of specific CTL would be unlikely. Predominantly CD8+ T-cell lines generated from PBMC by nonspecific stimulation with PHA and IL-2 were screened after three to four weeks of culture for cytolytic activity against autologous targets infected with vaccinia vectors encoding envLAI, RT, gag, and lacZ control. A strong gp 160-specific CTL response was detected in two vaccines in the recombinant vaccinia plus subunit boost study. Modest responses were seen in four of the other five live vector-primed vaccinees. No significant gp160-specific CTL were observed in three volunteers given only subunit rgp160 or in five control subjects.
Perales
M A
MA
Department of Medicine, New England Medical Center, Boston, MA, USA.
Schwartz
D H
DH
Fabry
J A
JA
Lieberman
J
J
D016915:AIDS Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002857:Chromium / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D018023:HIV Seronegativity; D006801:Humans; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014614:Vaccines, Synthetic; D002857:Chromium