Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group.
OBJECTIVE
To determine the ability of live attenuated canarypox virus expressing HIV antigens to induce CD8+ cytotoxic T-cell responses and to prime for neutralizing antibody responses to boosting with purified recombinant gp120 subunit vaccine.


METHODS
A prospective, double-blind, randomized, immunogenicity and safety study was conducted in healthy adults at low risk for acquiring HIV infection and who were seronegative for HIV.


METHODS
CD8+ cytotoxic T-cells directed against Env or Gag expressing target cells were measured after live recombinant canarypox-HIV-1 vaccine priming (vaccine given at days 0, 7, 14 and 21). Neutralizing antibodies were measured after subunit boosting (vaccine given at days 28 and 84).


RESULTS
CD8+ CTL were induced in 64% of volunteers by the live recombinant canarypox-HIV-1 vaccine. All volunteers who received two doses of subunit vaccine after live recombinant canarypox priming developed neutralizing antibodies directed against laboratory strains of HIV-1 and seven out of eight volunteers tested developed neutralizing antibodies to the primary isolate, BZ167, but to none of eight other primary isolates. Unprimed controls had low or absent neutralizing antibodies after two doses of subunit vaccine.


CONCLUSIONS
The live canarypox vector was safe, stimulated cytotoxic T-cells and primed for a vigorous neutralizing antibody response upon boosting with subunit gp120 vaccine. This vaccine combination should be evaluated further for inducing protection against HIV infection.
Belshe
R B
RB
Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine and St. Louis Veterans Administration Medical Center, Missouri, USA.
Gorse
G J
GJ
Mulligan
M J
MJ
Evans
T G
TG
Keefer
M C
MC
Excler
J L
JL
Duliege
A M
AM
Tartaglia
J
J
Cox
W I
WI
McNamara
J
J
Hwang
K L
KL
Bradney
A
A
Montefiori
D
D
Weinhold
K J
KJ
D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D018150:Avipoxvirus / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D004311:Double-Blind Method; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D008875:Middle Aged; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic
D016915:AIDS Vaccines; C106488:ALVAC-HIV-1 vCP250; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D014614:Vaccines, Synthetic