Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials.
BACKGROUND
A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in a community-based population in Thailand (RV144 trial). No protection was observed in Thai injection drug users who received AIDSVAX B/E alone (Vax003 trial). We compared the neutralizing antibody response in these 2 trials.


METHODS
Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells.


RESULTS
Neutralization of several tier 1 viruses was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and waned rapidly in both trials. The response in RV144 was targeted in part to V3 of gp120.vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120 protein inoculations alone, confirming a priming effect for vCP1521. Sporadic weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells.


CONCLUSIONS
The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies.
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. monte@duke.edu
David C
DC
Montefiori
Chitraporn
C
Karnasuta
Ying
Y
Huang
Hasan
H
Ahmed
Peter
P
Gilbert
Mark S
MS
de Souza
Robert
R
McLinden
Sodsai
S
Tovanabutra
Agnes
A
Laurence-Chenine
Eric
E
Sanders-Buell
M Anthony
MA
Moody
Mattia
M
Bonsignori
Christina
C
Ochsenbauer
John
J
Kappes
Haili
H
Tang
Kelli
K
Greene
Hongmei
H
Gao
Celia C
CC
LaBranche
Charla
C
Andrews
Victoria R
VR
Polonis
Supachai
S
Rerks-Ngarm
Punnee
P
Pitisuttithum
Sorachai
S
Nitayaphan
Jaranit
J
Kaewkungwal
Steve G
SG
Self
Phillip W
PW
Berman
Donald
D
Francis
Faruk
F
Sinangil
Carter
C
Lee
Jim
J
Tartaglia
Merlin L
ML
Robb
Barton F
BF
Haynes
Nelson L
NL
Michael
Jerome H
JH
Kim
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood*; D028121:Canarypox virus; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D015819:Substance Abuse, Intravenous; D013785:Thailand / Q000453:epidemiology
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins