Journal
SCIENCE
Volume 329, Issue 5993, Pages 856-861Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1187659
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Funding
- Vaccine Research Center
- Division of Clinical Research
- Laboratory of Immunoregulation of National Institute of Allergy and Infectious Diseases, NIH
- Bill and Melinda Gates Foundation
- International AIDS Vaccine Initiative
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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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