PubMed ID

22284192

UMMS Affiliation

Program in Molecular Medicine

Date

1-27-2012

Document Type

Article

Subjects

Antibodies, Monoclonal; Antigens, CD4; HIV Antibodies; HIV Envelope Protein gp120; HIV-1; Humans; Protein Binding; Receptors, HIV

Disciplines

Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences | Virology

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.

Comments

Citation: Retrovirology. 2012 Jan 27;9:9. Link to article on publisher's site

© 2012 Dueñas-Decamp et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Related Resources

Link to Article in PubMed

 
 

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