Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus.
The induction of human immunodeficiency virus (HIV)-specific T-cell responses is widely seen as critical to the development of effective immunity to HIV type 1 (HIV-1). Plasmid DNA and recombinant fowlpox virus (rFPV) vaccines are among the most promising safe HIV-1 vaccine candidates. However, the immunity induced by either vaccine alone may be insufficient to provide durable protection against HIV-1 infection. We evaluated a consecutive immunization strategy involving priming with DNA and boosting with rFPV vaccines encoding common HIV-1 antigens. In mice, this approach induced greater HIV-1-specific immunity than either vector alone and protected mice from challenge with a recombinant vaccinia virus expressing HIV-1 antigens. In macaques, a dramatic boosting effect on DNA vaccine-primed HIV-1-specific helper and cytotoxic T-lymphocyte responses, but a decline in HIV-1 antibody titers, was observed following rFPV immunization. The vaccine regimen protected macaques from an intravenous HIV-1 challenge, with the resistance most likely mediated by T-cell responses. These studies suggest a safe strategy for the enhanced generation of T-cell-mediated protective immunity to HIV-1.
Kent
S J
SJ
AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield 3078, Victoria, Australia. kent@burnet.edu.au
Zhao
A
A
Best
S J
SJ
Chandler
J D
JD
Boyle
D B
DB
Ramshaw
I A
IA
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D004279:DNA, Viral / Q000008:administration & dosage / Q000235:genetics; D005587:Fowlpox virus / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens / Q000008:administration & dosage / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D008254:Macaca nemestrina; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics
D016915:AIDS Vaccines; D004279:DNA, Viral; D015483:HIV Antibodies; D015488:HIV Antigens; D019444:Vaccines, DNA; D014765:Viral Vaccines