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Antimicrob. Agents Chemother. doi:10.1128/AAC.01528-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A high affinity, human-like antibody fragment (scFv) neutralising the lethal factor (LF) of Bacillus anthracis by inhibiting PA-LF complex formation

Groupe de biotechnologie des anticorps, Département de biologie des agents transmissibles, Centre de Recherche du Service de Santé des Armées, La Tronche, France; Institut für Biochemie und Biotechnologie, Technische Universität Braunschweig, Germany; Laboratoire d'ImmunoGénétique Moléculaire, LIGM, Université Montpellier II, UPR CNRS 1142, Institut de Génétique Humaine, IGH, Montpellier, France, and Institut Universitaire de France, Paris, France

^* To whom correspondence should be addressed. Email: pthullier{at}yahoo.com.

	Abstract

The anthrax lethal toxin (LT) consists of two subunits, the protective antigen (PA) and the lethal factor (LF), and is essential for anthrax pathogenesis. Several recombinant antibodies directed against PA and intended for medical use have been obtained, but none against LF despite the recommendations of anthrax experts. Here, we describe an anti-LF scFv that originated from an immunized macaque (Macaca fascicularis) and was obtained by phage display. Panning of the 1.8x10⁸ clones library allowed the isolation of 2LF, a high affinity (KD =1.02 nM) scFv, which is highly neutralizing in the standardized in vitro (IC50 = 1.20 ± 0.06 nM) and in an in vivo assays. The scFv neutralizes anthrax lethal toxin by inhibiting the formation of the LF-PA complex. The genes encoding 2LF are very similar to those of human immunoglobulin germline genes, sharing substantial (84.2 %) identity with their most similar, germinally encoded counterparts; this feature favours medical applications. These results, and others formerly published, demonstrate that our approach can generate antibody fragments suitable for prophylaxis and therapeutics.

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