Ascione, A. and Capecchi, B. and Campitelli, L. and Imperiale, V. and Flego, M. and Zamboni, S. and Gellini, M. and Alberini, I. and Pittiglio, E. and Donatelli, I. and Temperton, N.J. and Cianfriglia, M. (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.
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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. Â© 2009 Elsevier B.V. All rights reserved.
|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:||03 Aug 2012 11:50|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/29991 (The current URI for this page, for reference purposes)|
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