Other

University of Glasgow

Timothy John Mitchell

Lea-Ann Kirkham

James Cleland Paton

Gillian Douce

David John Hansman

John Arthur Walker

Graeme James Cowan

Peter William Andrew

Graham John Boulnois

The invention relates to the use of bacterial cytolysin proteins, such as pneumolysin, as adjuvants for stimulating or enhancing immune responses against co-administered target antigens. Desirably, the target antigen is provided as a fusion protein with the cytolysin. The inventors have found that cytolysins may be particularly effective for stimulation of mucosal immune responses against the target antigen.

Adjuvant compounds

The invention relates to immunogenic compositions comprising mutantpneumolysin proteins. The invention further relates to such proteins and nucleic acids encoding these proteins. In particular embodiments, the invention is directed to an isolated mutant pneumolysin (PLY) protein, wherein the mutant PLY protein differs from the wild-type PLY protein of SEQ ID NO:1 presence of a mutation within the region of amino acids 144 to 161 of the wild type such that the toxicity of the mutant is reduced relative to that of the wild-type protein. In particular embodiments, the mutant PLY protein differs from the wild-type protein by the substitution or deletion of amino acids including the deletion of two adjacent amino acids within the region of amino acids 144 to 151 of the wild-type sequence.

Mutant pneumolysin proteins

Mutants of pneumolysin that are non-toxic by reason of amino acid substitutions have been constructed. These mutants elicit an immune response in animals that is reactive to wild-type pneumolysin. The invention also encompasses vaccines for humans based on these mutants, including vaccines comprising conjugates with pneumococcal capsular polysaccharides.

Pneumolysin mutants and pneumococcal vaccines made therefrom

Growing community of inventors

Glasgow, United Kingdom

Timothy John Mitchell