Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10.

ABSTRACT: Monoclonal antibodies b12 and 4E10 are broadly neutralizing against a variety of strains of the human immunodeficiency virus type 1 (HIV-1). The epitope for b12 maps to the CD4-binding site in the gp120 subunit of HIV-1's trimeric gp120-gp41 envelope spike, whereas 4E10 recognizes the membrane-proximal external region (MPER) of gp41. Here, we constructed and compared a series of architectures for the b12 and 4E10 combining sites that differed in size, valency, and flexibility. In a comparative analysis of the ability of the b12 and 4E10 constructs to neutralize a panel of clade B HIV-1 strains, we observed that the ability of bivalent constructs to cross-link envelope spikes on the virion surface made a greater contribution to neutralization by b12 than by 4E10. Increased distance and flex

SUBMITTER: Klein JS 

PROVIDER: S-EPMC2678646 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature