Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial.
BACKGROUND
A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would "qualify" for a trial to define a correlate of efficacy.


METHODS
A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISpot) assay.


RESULTS
Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57% (95% confidence interval [CI]: 40% to 71%) to 94% (95% CI: 85% to 99%). Net cumulative HIV-specific CD8 IFNgamma ELISpot assay responses were 13% (95% CI: -1% to 26%) for recipients of vCP1452 alone and 16% (95% CI: 2% to 29%) for recipients of vCP1452 plus rgp120.


CONCLUSIONS
Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30%.
Russell
Nina D
ND
Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. nina.russell@gatesfoundation.org
Graham
Barney S
BS
Keefer
Michael C
MC
McElrath
M Juliana
MJ
Self
Steve G
SG
Weinhold
Kent J
KJ
Montefiori
David C
DC
Ferrari
Guido
G
Horton
Helen
H
Tomaras
Georgia D
GD
Gurunathan
Sanjay
S
Baglyos
Lynn
L
Frey
Sharon E
SE
Mulligan
Mark J
MJ
Harro
Clayton D
CD
Buchbinder
Susan P
SP
Baden
Lindsey R
LR
Blattner
William A
WA
Koblin
Beryl A
BA
Corey
Lawrence
L
D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D028121:Canarypox virus / Q000235:genetics; D002857:Chromium / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
D016915:AIDS Vaccines; C112734:AIDSVAX; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D002857:Chromium; D007371:Interferon-gamma