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Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity.
- Source :
- Nature Biotechnology; Nov2013, Vol. 31 Issue 11, p1047-1052, 6p
- Publication Year :
- 2013
-
Abstract
- Ibalizumab is a humanized monoclonal antibody that binds human CD4-a key receptor for HIV-and blocks HIV-1 infection. However, HIV-1 strains with mutations resulting in loss of an N-linked glycan from the V5 loop of the envelope glycoprotein gp120 are resistant to ibalizumab. Previous structural analysis suggests that this glycan fills a void between the gp120 V5 loop and the ibalizumab light chain, perhaps causing steric hindrance that disrupts viral entry. If this void contributes to HIV-1 resistance to ibalizumab, we reasoned that 'refilling' it by engineering an N-linked glycan into the ibalizumab light chain at a position spatially proximal to gp120 V5 may restore susceptibility to ibalizumab. Indeed, one such ibalizumab variant neutralized 100% of 118 diverse HIV-1 strains tested in vitro, including 10 strains resistant to parental ibalizumab. These findings demonstrate that the strategic placement of a glycan in the variable region of a monoclonal antibody can substantially enhance its activity. [ABSTRACT FROM AUTHOR]
- Subjects :
- GLYCANS
MONOCLONAL antibodies
HIV
HIV infections
GENETIC mutation
GLYCOPROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 10870156
- Volume :
- 31
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Nature Biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 91895767
- Full Text :
- https://doi.org/10.1038/nbt.2677