Kumar, R., Kumari, R., Khan, L., Sankhyan, A., Parray, H. A., Tiwari, A., Wig, N., Sinha, S. and Luthra, K. (2018) Isolation and characterization of cross-neutralizing human anti-V3 single-chain variable fragments (scFvs) against HIV-1 from an antigen preselected phage library. Applied Biochemistry and Biotechnology, 187(3), pp. 1011-1027. (doi: 10.1007/s12010-018-2862-8) (PMID:30151637)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kumari, Dr Ruchi |
| Authors: | Kumar, R., Kumari, R., Khan, L., Sankhyan, A., Parray, H. A., Tiwari, A., Wig, N., Sinha, S., and Luthra, K. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Applied Biochemistry and Biotechnology |
| Publisher: | Springer |
| ISSN: | 0273-2289 |
| ISSN (Online): | 1559-0291 |
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