近日，德国科隆大学Florian Klein小组研发出一个具有广泛效力中和抗体，可实现对HIV-1的逃逸限制。这一研究成果于2020年2月6日刊发在国际学术期刊《细胞》上。

Title: Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody

Author: Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jrg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Ftkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, Florian Klein

Issue&Volume: January 30, 2020

Abstract: Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5- cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.

DOI: 10.1016/j.cell.2020.01.010

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30057-X