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Neutralizing antibodies against botulinum toxins A,B,E

Objective

Botulinum neurotoxins (BoNTs), the most toxic substances known, are susceptible for use as bioweapons (listed as class A agents by CDC). Currently licensed animal derived antibodies or F(ab’)2 preparations, are at a high risk of inducing adverse effects and their privately-owned stockpiles are limited. In this project, we will target the most lethal types of BoNTs: A (subtypes A1 and A2), B (B1 and B2) and E (E1). The antibodies will be directed against the C-terminus of the heavy chain and the light chain of each of these three BoNTs, as these domains contain neutralizing epitopes, according to the latest scientific data. The six corresponding immunogens will be produced in recombinant form, and utilized to immunize macaques (Macaca fascicularis), from which phage-displayed immune libraries will be built. Utilizing the phage technology, scFvs cross- reacting with A1 and A2, or B1 and B2subtypes will be panned. The best scFv from each library will be selected according to its high affinity and in vitro neutralization property. The six most neutralizing scFvs will then be super-humanized (“germline-humanized”) and expressed as IgGs, which will be tested in vivo, in a standardised model of protection and against toxins obtained from collections of clostridia strains. The project includes representatives of medical first-responders who will disseminate our results, and help create a market so that the necessary clinical studies could be performed in future. The project will offer an unequalled level of security against biothreats in Europe, based upon a family of well-tolerated and effective molecules.
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Coordinator

MINISTERE DE LA DEFENSE

Address

Rue Saint Dominique, 14
75007 Paris

France

Activity type

Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)

EU Contribution

€ 136 000

Administrative Contact

Jean-Nicolas Tournier (Prof.)

Participants (9)

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Centre de Recherche du Service de Santé des Armées

France

EU Contribution

€ 549 500

TECHNISCHE UNIVERSITAET BRAUNSCHWEIG

Germany

EU Contribution

€ 418 360

INSTITUT PASTEUR

France

EU Contribution

€ 597 800

Public Health England an Executive Agency of the Dept of Health

United Kingdom

EU Contribution

€ 314 190,60

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 139 440

LFB-BIOTECHNOLOGIES

France

EU Contribution

€ 133 081

HELSINGIN YLIOPISTO

Finland

EU Contribution

€ 250 069,60

ABSISKEY CP

France

EU Contribution

€ 152 500

Medicines and Healthcare products Regulatory Agency

United Kingdom

EU Contribution

€ 275 444,80

Project information

Grant agreement ID: 241832

Status

Closed project

  • Start date

    1 September 2010

  • End date

    28 February 2015

Funded under:

FP7-SECURITY

  • Overall budget:

    € 3 896 416,21

  • EU contribution

    € 2 966 386

Coordinated by:

MINISTERE DE LA DEFENSE

France