Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1

Ascione, Alessandro and Capecchi, Barbara and Campitelli, Laura and Imperiale, Valentina and Flego, Michela and Zamboni, Silvia and Gellini, Mara and Alberini, Isabella and Pittiglio, Eliana and Donatelli, Isabella and Temperton, Nigel J. and Cianfriglia, Maurizio (2009) Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1. Antiviral Research, 83 (3). pp. 238-244. ISSN 0166-3542. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Effective diagnostic and therapeutic strategies are needed to control and combat the highly pathogenic avian influenza virus (AIV) subtype H5N1. To this end, we developed human monoclonal antibodies (mAbs) in single chain fragment variable (scFv) format towards the H5N1 avian influenza virus to gain new insights for the development of immunotherapy against human cases of H5N1. Using a biopanning based approach a large array of scFvs against H5N1 virus were isolated from the human semi-synthetic ETH-2 phage antibody library. H5N1 ELISA-positive scFvs with unique variable heavy (VH) and light (VL) chain gene sequences showed different biochemical properties and neutralization activity across H5N1 viral strains. In particular, the scFv clones AV.D1 and AV.C4 exerted a significant inhibition of the H5N1 A/Vietnam/1194/2004 virus infection in a pseudotype-based neutralization assay. Interestingly, these two scFvs displayed a cross-clade neutralizing activity versus A/whooping swan/Mongolia/244/2005 and A/Indonesia/5/2005 strains. These studies provide proof of the concept that human mAbs in scFv format with well-defined H5N1 recognition patterns and in vitro neutralizing activity can be easily and rapidly isolated by biopanning selection of an entirely artificial antibody repertoire using inactivated H5N1 virus as a bait. © 2009 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled keywords: Avian influenza, H5N1 virus, Immunoprophylaxis, Neutralizing mAbs, scFv, immunoglobulin heavy chain, immunoglobulin light chain, luciferase, monoclonal antibody, single chain fragment variable antibody, antibody isolation, article, biochemistry, biopanning, cladistics, controlled study, enzyme linked immunosorbent assay, gene sequence, immunotherapy, in vitro study, Indonesia, Influenza virus A H1N1, Influenza virus A H3N2, Influenza virus A H5N1, Influenza virus A H5N2, molecular recognition, Mongolia, nonhuman, phage display, priority journal, strain difference, Viet Nam, virus inactivation, virus inhibition, virus neutralization, virus strain, Antibodies, Monoclonal, Antibodies, Viral, Humans, Immunoglobulin Variable Region, Indonesia, Influenza A Virus, H5N1 Subtype, Influenza, Human, Mongolia, Neutralization Tests, Orthomyxoviridae, Peptide Library, Vietnam, Aves, Avian influenza virus, Orthomyxoviridae
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 02 Aug 2012 10:01
Last Modified: 22 Apr 2014 11:26
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