Abstract
BackgroundThe 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.FindingsAll 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.ConclusionsOur 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.
Highlights
The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for vaccines
Our data indicate that the b12 W100 pocket on gp120 is infrequently targeted by CD4bs mabs
The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for the development of vaccines that aim to elicit neutralizing antibodies effective against diverse HIV-1 strains
Summary
The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for vaccines. We showed previously that the presence of a combination of an arginine at residue 373 and a glycan at N386 appears to block the pocket and confer robust resistance to b12 for all five primary HIV-1 envelopes tested [1]. * Correspondence: paul.clapham@umassmed.edu 1Center for AIDS Research, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, MA 01605 Full list of author information is available at the end of the article envelope of the T-cell line adapted NL4.3 strain became resistant when carrying the R373/N386 glycan combination.
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