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Isolation and Characterization of Cross-Neutralizing Human Anti-V3 Single-Chain Variable Fragments (scFvs) Against HIV-1 from an Antigen Preselected Phage Library

Author:
Kumar, Rajesh, Kumari, Ruchi, Khan, Lubina, Sankhyan, Anurag, Parray, Hilal Ahmad, Tiwari, Ashutosh, Wig, Naveet, Sinha, Subrata, Luthra, Kalpana
Source:
Applied biochemistry and biotechnology 2019 v.187 no.3 pp. 1011-1027
ISSN:
0273-2289
Subject:
DNA libraries, HIV infections, Human gammaherpesvirus 4, Human immunodeficiency virus 1, antiretroviral agents, bacteriophages, binding sites, disease course, epitopes, humans, immunotherapy, molecular models, monoclonal antibodies, mononuclear leukocytes, neutralizing antibodies, peptides, protective effect
Abstract:
Recently conducted human phase- I trials showed protective effect of anti-HIV-1 broadly neutralizing antibodies (bnAbs). The V3 region of the HIV-1 envelope is highly conserved as it is the co-receptor binding site, and is highly immunogenic. Recombinant single-chain antibody fragments (scFvs) can serve as potential tools for construction of chimeric/bispecific antibodies that can target different epitopes on the HIV-1 envelope. Previously, we have constructed a V3 specific human scFv phage recombinant library by a combinational approach of Epstein–Barr virus (EBV) transformation and antigen (V3) preselection, using peripheral blood mononuclear cells (PBMCs), from a subtype C HIV-1 infected antiretroviral naive donor. In the present study, by biopanning this recombinant scFv phage library with V3B (subtype B) and V3C (subtype C) peptides, we identified unique cross reactive anti-V3 scFv monoclonals. These scFvs demonstrated cross-neutralizing activity when tested against subtype A, subtype B, and subtype C viruses. Further, molecular modeling of the anti-V3 scFvs with V3C and V3B peptides predicted their sites of interaction with the scFvs, providing insights for future immunogen design studies. A large collection of such monoclonal antibody fragments with diverse epitope specificities can be useful immunotherapeutic reagents along with antiretroviral drugs to prevent HIV-1 infection and disease progression.
Agid:
6354512