Extensively cross-reactive anti-HIV-1 neutralizing antibodies induced by gp140 immunization.
An immunization regimen was evaluated in rabbits consisting of the soluble, oligomeric form of envelope glycoprotein of HIV-1, strain R2 (gp140(R2)), or the surface component of the same envelope (Env), gp120(R2), in the adjuvant AS02A. The gp140(R2) was selected based on its unusual CD4-independent phenotype and the exceptionally broad neutralizing response in the infected donor. The gp140(R2) immunogen induced antibodies that achieved 50% neutralization of 48/48, and 80% neutralization of 43/46 primary strains of diverse HIV-1 subtypes tested. The strains tested included members of standard panels of subtype B and C strains, and other diverse strains known to be neutralization resistant. The gp120(R2) induced antibodies that neutralized 9/48 of the same strains. Neutralization was IgG-mediated and HIV-1-specific. These results demonstrate that induction of truly broad spectrum neutralizing antibodies is an achievable goal in HIV-1 vaccine development.
Zhang
Peng Fei
PF
Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Cham
Fatim
F
Dong
Ming
M
Choudhary
Anil
A
Bouma
Peter
P
Zhang
Zhiqiang
Z
Shao
Yiming
Y
Feng
Yan-Ru
YR
Wang
Lemin
L
Mathy
Nathalie
N
Voss
Gerald
G
Broder
Christopher C
CC
Quinnan
Gerald V
GV
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000918:Antibody Specificity; D003429:Cross Reactions; D015686:Gene Products, env / Q000008:administration & dosage / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D009500:Neutralization Tests; D011817:Rabbits; D014611:Vaccination; D054299:env Gene Products, Human Immunodeficiency Virus
D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D015483:HIV Antibodies; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1