Zhang Peng Fei, Cham Fatim, Dong Ming, Choudhary Anil, Bouma Peter, Zhang Zhiqiang, Shao Yiming, Feng Yan-Ru, Wang Lemin, Mathy Nathalie, Voss Gerald, Broder Christopher C, Quinnan Gerald V
Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10193-8. doi: 10.1073/pnas.0608635104. Epub 2007 May 31.
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.
在兔中评估了一种免疫方案,该方案由HIV-1 R2株包膜糖蛋白的可溶性寡聚形式(gp140(R2))或相同包膜(Env)的表面成分gp120(R2)与佐剂AS02A组成。选择gp140(R2)是基于其不寻常的不依赖CD4的表型以及在受感染供体中异常广泛的中和反应。gp140(R2)免疫原诱导的抗体对所测试的48/48种HIV-1不同亚型的原代毒株实现了50%的中和,对43/46种实现了80%的中和。所测试的毒株包括B和C亚型标准毒株组的成员以及其他已知具有中和抗性的不同毒株。gp120(R2)诱导的抗体对相同毒株中的9/48种具有中和作用。中和作用是由IgG介导的且具有HIV-1特异性。这些结果表明,诱导真正广谱的中和抗体在HIV-1疫苗开发中是一个可以实现的目标。