ANTIBOTABE
"Neutralizing antibodies against botulinum toxins A,B,E"
| Coordinatore | MINISTERE DE LA DEFENSE
Organization address
address: "Rue Saint Dominique, 14" contact info |
| Nazionalità Coordinatore | France [FR] |
| Totale costo | 3˙896˙416 € |
| EC contributo | 2˙966˙386 € |
| Programma | FP7-SECURITY
Specific Programme "Cooperation": Security |
| Code Call | FP7-SEC-2009-1 |
| Funding Scheme | CP |
| Anno di inizio | 2010 |
| Periodo (anno-mese-giorno) | 2010-09-01 - 2015-02-28 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
MINISTERE DE LA DEFENSE
Organization address
address: "Rue Saint Dominique, 14" contact info |
FR (PARIS) | coordinator | 136˙000.00 |
| 2 |
INSTITUT PASTEUR
Organization address
address: RUE DU DOCTEUR ROUX 25-28 contact info |
FR (PARIS CEDEX 15) | participant | 597˙800.00 |
| 3 |
Nome Ente NON disponibile
Organization address
city: La Tronche contact info |
FR (La Tronche) | participant | 549˙500.00 |
| 4 |
TECHNISCHE UNIVERSITAT BRAUNSCHWEIG
Organization address
address: POCKELSSTRASSE 14 contact info |
DE (BRAUNSCHWEIG) | participant | 418˙360.00 |
| 5 |
HEALTH PROTECTION AGENCY HPA
Organization address
address: Central Office - 7th Floor, Holborn Gate - High Holborn 330 contact info |
UK (LONDON) | participant | 314˙190.60 |
| 6 |
Department of Health
Organization address
address: "Quarry House, Quarry Hill" contact info |
UK (Leeds) | participant | 275˙444.80 |
| 7 |
HELSINGIN YLIOPISTO
Organization address
address: YLIOPISTONKATU 4 contact info |
FI (HELSINGIN YLIOPISTO) | participant | 250˙069.60 |
| 8 |
ABSISKEY CP
Organization address
address: RUE COLONEL DUMONT 26 contact info |
FR (GRENOBLE) | participant | 152˙500.00 |
| 9 |
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Organization address
address: Rue Michel -Ange 3 contact info |
FR (PARIS) | participant | 139˙440.00 |
| 10 |
LFB-BIOTECHNOLOGIES
Organization address
address: "AVENUE DES TROPIQUES, ZA DE COURTABOEUF 3" contact info |
FR (LES ULIS) | participant | 133˙081.00 |
Mappa
Word cloud
Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.
Obiettivo del progetto (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.'
Introduzione (Teaser)
Botulinum toxins are extremely potent molecules used in medicine that can also be exploited in terrorist attacks. To neutralise the impact of these deadly substances, EU researchers are in the process of developing antibodies as a prophylactic or therapeutic intervention.
Descrizione progetto (Article)
Botulinum toxins are produced by the bacterium Clostridium botulinum and are among the most toxic substances known. They work by blocking muscle contraction and show numerous therapeutic benefits in muscular disorders such as dystonias.
Currently, commercially available antibodies raised in animals constitute the only option against botulism in life-threatening situations. Such antibodies have limitations in performance and undesirable side-effects.
Scientists on the EU-funded 'Neutralizing antibodies against botulinum toxins A,B,E' (http://www.antibotabe.eu (ANTIBOTABE)) project are looking for alternative solutions. Instead of isolating antibodies from the serum of vaccinated animals, they have decided to produce recombinant antibodies in vitro. These antibodies would minimise any immune side-effects and they could be engineered to target any desired part of the neurotoxin.
After characterising all toxin subtypes, scientists decided to generate antibodies against the most dominant subtypes of all three (A, B and E) classes of botulinum toxins. The antibody phage display method was used to genetically engineer bacteriophages (viruses that infect bacteria) to express antibodies against the desired molecules. Selection of antibodies with the highest affinity takes place through rounds of binding onto immobilised targets.
Ongoing work has already produced antibodies with promising neutralising capacities, especially some that are designed against the enzymatically active portion of the toxin. Although validation by the European Medicines Agency would be required before these antibodies are approved for human use, ANTIBOTABE could provide more efficient alternatives against bioterrorism.