Pathobiology and Immunology Division, Oregon National Primate Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Curr HIV/AIDS Rep. 2012 Mar;9(1):64-72. doi: 10.1007/s11904-011-0105-5.
It is now evident that powerful antibodies directed to conserved regions of HIV-1 envelope protein develop during chronic infection in some individuals and that these antibodies can neutralize a broad array of diverse isolates in vitro, so termed broadly neutralizing antibodies (bNAbs). A great deal of effort is directed internationally at understanding the ontogeny of NAbs during infection as well as in designing and testing immunogens that can elicit bNAbs in animal models and in humans. Given the parrying tactics of Env, multiple approaches, along with high-resolution structural studies, will be needed to reach a degree of understanding sufficient to design an effective vaccine. We discuss and note here some of the most important recent advances in our knowledge of how neutralizing antibodies develop in vivo, the recent discovery of extremely powerful neutralizing monoclonal antibodies isolated from natural infection, enhanced methodologies that have accelerated discoveries on both fronts, and the progress made in eliciting potent NAbs with limited breadth by vaccination.
现在很明显,在一些慢性感染个体中,针对 HIV-1 包膜蛋白保守区域的强大抗体得以产生,这些抗体可以在体外中和广泛的不同分离株,因此被称为广泛中和抗体(bNAb)。国际上投入了大量精力来了解感染过程中 NAb 的发生情况,以及设计和测试免疫原,以在动物模型和人类中诱导出 bNAb。鉴于 Env 的规避策略,需要多种方法以及高分辨率结构研究,才能达到足以设计有效疫苗的理解程度。我们在这里讨论并指出了我们对体内中和抗体如何产生的认识的一些最新进展,最近从自然感染中分离出的极其强大的中和单克隆抗体的发现,加速了这两个方面发现的增强方法,以及通过接种疫苗引起有限广谱的有效 NAb 所取得的进展。