Abstract:
:Anti-human immunodeficiency virus type 1 (HIV-1) antibodies whose binding to gp120 is enhanced by CD4 binding (CD4i antibodies) are generally considered nonneutralizing for primary HIV-1 isolates. However, a novel CD4i-specific Fab fragment, X5, has recently been found to neutralize a wide range of primary isolates. To investigate the precise nature of the extraordinary neutralizing ability of Fab X5, we evaluated the abilities of different forms (immunoglobulin G [IgG], Fab, and single-chain Fv) of X5 and other CD4i monoclonal antibodies to neutralize a range of primary HIV-1 isolates. Our results show that, for a number of isolates, the size of the neutralizing agent is inversely correlated with its ability to neutralize. Thus, the poor ability of CD4i-specific antibodies to neutralize primary isolates is due, at least in part, to steric factors that limit antibody access to the gp120 epitopes. Studies of temperature-regulated neutralization or fusion-arrested intermediates suggest that the steric effects are important in limiting the binding of IgG to the viral envelope glycoproteins after HIV-1 has engaged CD4 on the target cell membrane. The results identify hurdles in using CD4i epitopes as targets for antibody-mediated neutralization in vaccine design but also indicate that the CD4i regions could be efficiently targeted by small molecule entry inhibitors.
journal_name
J Viroljournal_title
Journal of virologyauthors
Labrijn AF,Poignard P,Raja A,Zwick MB,Delgado K,Franti M,Binley J,Vivona V,Grundner C,Huang CC,Venturi M,Petropoulos CJ,Wrin T,Dimitrov DS,Robinson J,Kwong PD,Wyatt RT,Sodroski J,Burton DRdoi
10.1128/jvi.77.19.10557-10565.2003subject
Has Abstractpub_date
2003-10-01 00:00:00pages
10557-65issue
19eissn
0022-538Xissn
1098-5514journal_volume
77pub_type
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