Program in Molecular Medicine
Antibodies, Monoclonal; Antigens, CD4; HIV Antibodies; HIV Envelope Protein gp120; HIV-1; Humans; Protein Binding; Receptors, HIV
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences | Virology
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.
Rights and Permissions
© 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.
DOI of Published Version
Retrovirology. 2012 Jan 27;9:9. Link to article on publisher's site
Duenas-Decamp, Maria J.; O'Connell, Olivia J.; Corti, Davide; Zolla-Pazner, Susan; and Clapham, Paul R., "The W100 pocket on HIV-1 gp120 penetrated by b12 is not a target for other CD4bs monoclonal antibodies" (2012). Open Access Articles. 2326.