University of Exeter

Biosystems Technology Limited

One Health Ventures Ltd

Universiteit Gent

Richard W Titball

Richard Ducatelle

Filip Van Immerseel

Claire Naylor

Ajit Basak

Olivia Champion

Sergio Paulo Fernandes Da Costa

Monika Bokori-Brown

Sérgio Paulo Fernandes Da Costa

Monika Bokori-brown

Nicholas Peter Lewis

Helen Morcrette

Dorien Mot

This invention relates to methods and compositions for detecting, diagnosing, preventing, treating or ameliorating the symptoms of a demyelinating condition selected from: enterotoxemia (ET), multiple sclerosis (MS), clinically definite MS (CDMS), clinically isolated syndrome (CIS), neuromyelitis optica spectrum disorder (NMOSD), optic neuritis (ON), neuromyelitis optica (NMO), myelitis, myelitis, transverse myelitis (TM), a disease or condition characterised by the increase or presence of antibodies against aquaporin-4 (AQP-4) and/or astrocyte damage, and acute disseminated encephalomyelitis (ADEM) in a human or animal subject in need. The methods comprise administering to the subject a composition comprising an effective amount of an agent that directly or indirectly interferes with epsilon toxin (ETX) produced bytype B or type D bacterial strain, an ETX-binding receptor, or an interaction of ETX with its binding receptor so as to inhibit or suppress ETX modulated receptor signalling activities. The invention also provides novel polypeptides useful as a vaccine against diseases caused by or associated with the epsilon toxin of

Epsilon toxin from clostridium perfringens as a vaccine

There is provided a method or improving the surface sterility of an invertebrate organism having an external cuticle, comprising contacting an outer surface of the organism, or a portion thereof, with an aqueous alcohol solution of less than about 70% v/v for a period of less than 60 seconds. The method is especially useful to provide research-grade organisms which can be utilised in research involving injection of compositions through the external cuticle, by reducing phenotype changes resulting from introduction of surface contaminants into the interior of the organism.

Method for preparation of research organisms

There is provided a NetB epitope polypeptide comprising at least 10 contiguous amino acids from SEQ ID NO:1 and comprising a mutation in at least one position between amino acids 130 and 297 as compared with the equivalent position in SEQ ID NO:3, the mutation preferably being located within a rim domain, the polypeptide being capable of binding an antibody which binds to SEQ ID NO:1 and having reduced toxicity compared with the toxicity of SEQ ID NO:1. The polypeptide is useful to vaccinate a subject against infection by

Vaccine

There is provided an epsilon toxin epitope polypeptide comprising a sequence of at least 10 contiguous amino acids from SEQ ID NO:3, the sequence comprising a mutation of at least one tyrosine residue compared to the equivalent sequence in SEQ ID NO:3, the polypeptide being capable of binding an antibody which binds to SEQ ID NO:5 and having reduced toxicity compared with the toxicity of SEQ ID NO:5. The polypeptide is useful in a method of vaccinating a subject against developing a disease caused byand/or caused by (or associated with the presence of) active epsilon toxin.

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Exeter, United Kingdom

Richard W Titball