Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1
Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R Schief, Michael S Seaman, Tongqing Zhou, Stephen D Schmidt, Lan Wu, Ling Xu, Nancy S Longo, Krisha McKee, Sijy O'Dell, Mark K Louder, Diane L Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D Kwong, Mario Roederer, Richard T Wyatt, Gary J Nabel, John R Mascola, Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R Schief, Michael S Seaman, Tongqing Zhou, Stephen D Schmidt, Lan Wu, Ling Xu, Nancy S Longo, Krisha McKee, Sijy O'Dell, Mark K Louder, Diane L Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D Kwong, Mario Roederer, Richard T Wyatt, Gary J Nabel, John R Mascola
Abstract
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
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Source: PubMed