Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-seronegative Ugandan volunteers: results of the HIV Network for Prevention Trials 007 Vaccine Study.
In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients.
Cao
H
H
California Department of Health Services, Viral and Rickettsial Disease Laboratory, Richmond, CA 94804, USA. hcao@dhs.ca.gov
Kaleebu
P
P
Hom
D
D
Flores
J
J
Agrawal
D
D
Jones
N
N
Serwanga
J
J
Okello
M
M
Walker
C
C
Sheppard
H
H
El-Habib
R
R
Klein
M
M
Mbidde
E
E
Mugyenyi
P
P
Walker
B
B
Ellner
J
J
Mugerwa
R
R
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D028121:Canarypox virus / Q000235:genetics; D003429:Cross Reactions; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014454:Uganda; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA