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Open Access Short report

The W100 pocket on HIV-1 gp120 penetrated by b12 is not a target for other CD4bs monoclonal antibodies

Maria J Dueñas-Decamp1, Olivia J O'Connell1, Davide Corti2, Susan Zolla-Pazner3 and Paul R Clapham1*

Author Affiliations

1 Center for AIDS Research, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, MA 01605

2 Humabs Biomed SA, Bellinzona, CH-6500, Switzerland

3 Department of Pathology, New York University Langone School of Medicine, New York, NY 10016

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Retrovirology 2012, 9:9  doi:10.1186/1742-4690-9-9

Published: 27 January 2012

Abstract

Background

The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for vaccines. It is a priority to determine sites and structures within the CD4bs that are important for inclusion in vaccines. We studied a gp120 pocket penetrated by W100 of the potent CD4bs monoclonal antibody (mab), b12. We compared HIV-1 envelopes and corresponding mutants that carried blocked W100 pockets to evaluate whether other CD4bs mabs target this site.

Findings

All CD4bs mabs tested blocked soluble CD4 binding to gp120 consistent with their designation as CD4bs directed antibodies. All CD4bs mabs tested neutralized pseudovirions carrying NL4.3 wild type (wt) envelope. However, only b12 failed to neutralize pseudoviruses carrying mutant envelopes with a blocked W100 pocket. In addition, for CD4bs mabs that neutralized pseudovirions carrying primary envelopes, mutation of the W100 pocket had little or no effect on neutralization sensitivity.

Conclusions

Our data indicate that the b12 W100 pocket on gp120 is infrequently targeted by CD4bs mabs. This site is therefore not a priority for preservation in vaccines aiming to elicit antibodies targeting the CD4bs.

Keywords:
HIV; envelope; gp120; CD4 binding site; neutralization