Magnitude and breadth of a nonprotective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine.
BACKGROUND
A candidate vaccine consisting of human immunodeficiency virus type 1 (HIV-1) subunit gp120 protein was found previously to be nonprotective in an efficacy trial (Vax004) despite strong antibody responses against the vaccine antigens. Here we assessed the magnitude and breadth of neutralizing antibody responses in Vax004.


METHODS
Neutralizing antibodies were measured against highly sensitive (tier 1) and moderately sensitive (tier 2) strains of HIV-1 subtype B in 2 independent assays. Vaccine recipients were stratified by sex, race, and high versus low behavioral risk of HIV-1 acquisition.


RESULTS
Most vaccine recipients mounted potent neutralizing antibody responses against HIV-1(MN) and other tier 1 viruses. Occasional weak neutralizing activity was detected against tier 2 viruses. The response against tier 1 and tier 2 viruses was significantly stronger in women than in men. Race and behavioral risk of HIV-1 acquisition had no significant effect on the response. Prior vaccination had little effect on the neutralizing antibody response that arose after infection.


CONCLUSIONS
Weak overall neutralizing antibody responses against tier 2 viruses is consistent with a lack of protection in this trial. The magnitude and breadth of neutralization reported here should be useful for identifying improved vaccines.
Gilbert
Peter
P
Vaccine Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Wang
Maggie
M
Wrin
Terri
T
Petropoulos
Chris
C
Gurwith
Marc
M
Sinangil
Faruk
F
D'Souza
Patricia
P
Rodriguez-Chavez
Isaac R
IR
DeCamp
Allan
A
Giganti
Mike
M
Berman
Phillip W
PW
Self
Steve G
SG
Montefiori
David C
DC
D016915:AIDS Vaccines / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood*; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D009500:Neutralization Tests
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1