A new hope for an AIDS vaccine

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The mechanism by which HIV-1 eludes the human immune system is through a coat of human sugars. The antibody 2G12 has interlocking Fab arms which recognize the structural difference associated with the virus, effectively defeating the virus. The antibody, which was discovered 12 years ago, is found in a very few number of people found to be immune to HIV-1. This latest research, led by the Scripps Research Institute, identifies the precise mechanism by which 2G12 is effective, which may provide a template for synthesizing a vaccine.

 

The paper appears in the June 27th, 2003 issue of Science.

 

Abstract:

Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus type 1 (HIV-1) isolates by binding an unusually dense cluster of carbohydrate moieties on the "silent" face of the gp120 envelope glycoprotein. Crystal structures of Fab 2G12 and its complexes with the disaccharide Man:alpha:1-2Man and with the oligosaccharide Man₉GlcNAc₂ revealed that two Fabs assemble into an interlocked V_H domain-swapped dimer. Further biochemical, biophysical, and mutagenesis data strongly support a Fab-dimerized antibody as the prevalent form that recognizes gp120. The extraordinary configuration of this antibody provides an extended surface, with newly described binding sites, for multivalent interaction with a conserved cluster of oligomannose type sugars on the surface of gp120. The unique interdigitation of Fab domains within an antibody uncovers a previously unappreciated mechanism for high-affinity recognition of carbohydrate or other repeating epitopes on cell or microbial surfaces.