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Rapid induction of passive immunity against weapons of bioterrorism using transformed GRAS (generally regarded as safe) microorganisms

Objectif

Weapons of bioterrorism, such as the toxin-producing bacteria Bacillus anthracis and Clostridium botulinum, pose serious threats to Western societies. Since no products are available that allow rapid vaccination, exposed populations would be completely unp rotected. Even if a vaccine could be developed, active immunization would require multiple doses. Thereafter, it would take many months to achieve protective levels of antibodies and vaccination could only be applied to selected risk-groups. We have recent ly developed a model system in which Lactobacillus, a GRAS microorganism, can be transformed with antibody fragment encoding vectors. This allows the expression of functional single- chain antibodies against mucosal pathogens in situ. These antibody fragme nts retain their biological properties in vivo and may mitigate or prevent disease. The aim of this project is to select and characterize Lactobacilli with different tropisms and to develop the vector system currently used into a food-grade transformation/ integration/cleaning system that allows simultaneous expression of multiple antibody specificities. Furthermore, we intend to clone the genes encoding the variable region from hybridomas producing neutralizing antibodies against protective antigen (B. anth racis) and botulinum toxins (C. botulinum). These will be introduced into the selected Lactobacilli and the resulting transformants tested for their protective capacity in animal models. Our approach, which falls outside the domains of the FP6 thematic pri orities, represents a completely novel system for the induction of passive immunity that can be rapidly applied to populations at risk (for example through the drinking water). The transformed Lactobacilli will colonize the mucosa in exposed individuals, a llowing production of protective antibody fragments in situ. If successful, this project could be applied to therapy against a vast number of human/animal pathogens #

Appel à propositions

FP6-2003-NEST-A
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Coordinateur

KAROLINSKA INSTITUTET
Contribution de l’UE
Aucune donnée
Adresse
Nobels väg 1
STOCKHOLM
Suède

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Participants (3)