title: The W100 pocket on HIV-1 gp120 penetrated by b12 is not a target for other CD4bs monoclonal antibodies.
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.
  
  
  RESULTS
  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.
authors.affiliation: Center for AIDS Research, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, MA 01605, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Dueñas-Decamp
authors.forename: Olivia J
authors.initials: OJ
authors.lastname: O'Connell
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Paul R
authors.initials: PR
authors.lastname: Clapham
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011485:Protein Binding; D015728:Receptors, HIV / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; C514793:gp120 protein, Human immunodeficiency virus 1