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

被引：14

作者：

Ascione, Alessandro ^{[1
]}

Capecchi, Barbara ^{[2
]}

Campitelli, Laura ^{[3
]}

Imperiale, Valentina ^{[1
]}

Flego, Michela ^{[1
]}

Zamboni, Silvia ^{[1
]}

Gellini, Mara ^{[1
]}

Alberini, Isabella ^{[2
]}

Pittiglio, Eliana ^{[1
]}

Donatelli, Isabella ^{[3
]}

Temperton, Nigel J. ^{[4
,5
]}

Cianfriglia, Maurizio ^{[1
]}

机构：

[1] Ist Super Sanita, Dept Therapeut Res & Med Evaluat, I-00161 Rome, Italy

[2] Novartis Vaccines & Diagnost, I-53100 Siena, Italy

[3] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy

[4] UCL, Wohl Vir Ctr, London W1T 4JF, England

[5] UCL, Div Infect & Immun, London W1T 4JF, England

来源：

ANTIVIRAL RESEARCH | 2009年 / 83卷 / 03期

关键词：

Avian influenza; H5N1; virus; Immunoprophylaxis; Neutralizing mAbs; scFv; HEMAGGLUTININ; GENERATION; LIBRARIES; EPITOPES; THERAPY; DESIGN; UPDATE;

D O I：

10.1016/j.antiviral.2009.05.005

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：238 / 244

页数：7