Walker Laura M, Phogat Sanjay K, Chan-Hui Po-Ying, Wagner Denise, Phung Pham, Goss Julie L, Wrin Terri, Simek Melissa D, Fling Steven, Mitcham Jennifer L, Lehrman Jennifer K, Priddy Frances H, Olsen Ole A, Frey Steven M, Hammond Phillip W, Kaminsky Stephen, Zamb Timothy, Moyle Matthew, Koff Wayne C, Poignard Pascal, Burton Dennis R
Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.
Science. 2009 Oct 9;326(5950):285-9. doi: 10.1126/science.1178746. Epub 2009 Sep 3.
Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses.
广谱中和抗体(bNAbs)在一些感染HIV-1的个体中会随着时间的推移而产生,它为HIV疫苗设计确定了关键表位。我们采用系统方法,检测了约1800名主要感染非B亚型病毒的HIV-1感染者血清中的中和广度,并挑选供体来制备单克隆抗体(mAb)。然后,我们对来自一名感染A亚型的非洲供体的约30000个活化记忆B细胞的含抗体培养上清液进行了高通量中和筛选,以分离出两种靶向广谱中和表位的强效单克隆抗体。该表位优先在三聚体包膜蛋白上表达,跨越gp120亚基可变环的保守区域。这些结果为设计新的候选疫苗以引发bNAb反应提供了框架。