Cross-neutralization activity of single-chain variable fragment (scFv) derived from anti-V3 monoclonal antibodies mediated by post-attachment binding.

Cross-neutralization activity of single-chain variable fragment (scFv) derived from anti-V3 monoclonal antibodies mediated by post-attachment binding.
Jpn J Infect Dis. 2016 Feb 19;
Authors: Maruta Y, Kuwata T, Tanaka K, Alam M, Valdez KP, Egami Y, Suwa Y, Morioka H, Matsushita S
Abstract
The V3 loop in the envelope (Env) of HIV-1 is one of the major targets of neutralizing antibodies. However, this antigen is hidden inside the Env trimer in most isolates and is only fully exposed during CD4-gp120 interaction. Thus, primary HIV-1 isolates are relatively resistant to anti-V3 antibodies because IgG is too large to access the V3 loop. To overcome this obstacle, we constructed single-chain variable fragments (scFvs) from anti-V3 monoclonal antibodies 0.5γ, 5G2, and 16G6. Enhanced neutralization by 0.5γ and 5G2 scFvs was observed in strains that were resistant to their IgG counterparts. Neutralization coverage by 0.5γ scFv reached up to 90% of the tested viruses (tier 2 and 3 classes). The temperature-regulated neutralization assay revealed that the extensive cross-neutralization of 0.5γ scFv can be explained by its post-attachment neutralization. Results from neutralization assay using viruses with inter-subunit disulfide bond (SOS virus) suggested that the neutralization susceptible timeframe after attachment was between 60 and 120 min. These results indicate that the scFvs efficiently access the V3 loop and subsequently neutralize ...

Source: Japanese Journal of Infectious Diseases - February 19, 2016 Category: Infectious Diseases Authors: Maruta Y, Kuwata T, Tanaka K, Alam M, Valdez KP, Egami Y, Suwa Y, Morioka H, Matsushita S Tags: Jpn J Infect Dis Source Type: research