Cross-neutralizing anti-HIV-1 human single chain variable fragments(scFvs) against CD4 binding site and N332 glycan identified from a recombinant phage library

Khan, Lubina and Kumar, Rajesh and Thiruvengadam, Ramachandran and Parray, Hilal Ahmad and Makhdoomi, Muzamil Ashraf and Kumar, Sanjeev and Aggarwal, Heena and Mohata, Madhav and Hussain, Abdul Wahid and Das, Raksha and Varadarajan, Raghavan and Bhattacharya, Jayanta and Vajpayee, Madhu and Murugavel, K G and Solomon, Suniti and Sinha, Subrata and Luthra, Kalpana (2017) Cross-neutralizing anti-HIV-1 human single chain variable fragments(scFvs) against CD4 binding site and N332 glycan identified from a recombinant phage library. In: SCIENTIFIC REPORTS, 7 .

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Abstract

More than 50% of HIV-1 infection globally is caused by subtype_C viruses. Majority of the broadly neutralizing antibodies (bnAbs) targeting HIV-1 have been isolated from non-subtype_C infected donors. Mapping the epitope specificities of bnAbs provides useful information for vaccine design. Recombinant antibody technology enables generation of a large repertoire of monoclonals with diverse specificities. We constructed a phage recombinant single chain variable fragment (scFv) library with a diversity of 7.8 x 10(8) clones, using a novel strategy of pooling peripheral blood mononuclear cells (PBMCs) of six select HIV-1 chronically infected Indian donors whose plasma antibodies exhibited potent cross neutralization efficiency. The library was panned and screened by phage ELISA using trimeric recombinant proteins to identify viral envelope specific clones. Three scFv monoclonals D11, C11 and 1F6 selected from the library cross neutralized subtypes A, B and C viruses at concentrations ranging from 0.09 mu g/mL to 100 mu g/mL. The D11 and 1F6 scFvs competed with mAbs b12 and VRC01 demonstrating CD4bs specificity, while C11 demonstrated N332 specificity. This is the first study to identify cross neutralizing scFv monoclonals with CD4bs and N332 glycan specificities from India. Cross neutralizing anti-HIV-1 human scFv monoclonals can be potential candidates for passive immunotherapy and for guiding immunogen design.

Item Type:	Journal Article
Publication:	SCIENTIFIC REPORTS
Publisher:	NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Additional Information:	Copy right for the article belong to NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	14 Mar 2018 17:38
Last Modified:	14 Mar 2018 17:38
URI:	http://eprints.iisc.ac.in/id/eprint/59187

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