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

doi:10.1126/science.1187659

Cross-reactive neutralizing antibodies (NAbs) are found in thesera of many HIV-1тinfected subjects, but the virologicbasis of their neutralization remains poorly understood. Weused knowledge of HIV-1 envelope (Env) structure to developantigenically resurfaced glycoproteins specific for the structurallyconserved site of CD4 receptor binding. These probes were usedto identify sera with NAbs to the CD4-binding site (CD4bs) andto isolate individual B cells from such an HIV-1тinfecteddonor. By expressing immunoglobulin genes from individual cells,we identified three monoclonal antibodies, including a pairof somatic variants that neutralized over 90% of circulatingHIV-1 isolates. Exceptionally broad HIV-1 neutralization canbe achieved with individual antibodies targeted to the functionallyconserved CD4bs of gp120, an important insight for future HIV-1vaccine design.

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

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