July 17, 2011 - HIV-1 neutralizing antibodies presented by Ori

When: July 17, 2011 12:00
Where: Physics 377
Presenter: Ori Avi-No'am (Benjamin Podbilewicz lab, biology)
Link to paper: http://www.sciencemag.org/content/329/5993/856.full

Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1

Xueling Wu, 

 

Zhi-Yong Yang, 

 

Yuxing Li, ... 

Peter D. Kwong, Gary J. Nabel and 

John R. Mascola

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

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.