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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 (gp140R2), or the surface component of the same envelope (Env), gp120R2, in the adjuvant AS02A. The gp140R2 was selected based on its unusual CD4-independent phenotype and the exceptionally broad neutralizing response in the infected donor. The gp140R2 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 gp120R2 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.