Glaxo Wellcome Inc.

University Court of the University of Dundee

The Lister Institute of Preventive Medicine

The Royal Society

Burroughs Wellcome Co.

The Wellcome Foundation Limited

Steven Neville Chatfield

Ian George Charles

Gordan Dougan

Carlos Estenio Hormaeche

Kevin Stuart Johnson

Neil F Fairweather

Christopher Francis Higgins

Charles James Dorman

Gordon Dougan

Attenuated microorganism for use in immunoprophylaxis in which the attenuation is brought about by the presence of a mutation in the DNA sequence of the microorganism which encodes, or which regulates the expression of DNA encoding a protein that is produced in response to environmental stress, the microorganism optionally being capable of expressing DNA encoding a heterologous antigen.

Vaccines containing bacteria attenuated by mutation of the htrA gene

The present invention discloses a novel approach to attenuating bacteria and for their use as live vaccines. The vaccines can be used in human and animal medicine. In particular, there is disclosed a method of attenuating a bacteria by mutating a gene concerned with the regulation of one or more genes concerned with expression of outer membrane proteins, particularly porin proteins.

Live vaccines

An attenuated microorganism harboring two mutated genes, each of which is located in the organisms aromatic pathway is provided. These organisms can usefully form the basis of a vaccine. They can be genetically engineered so as to express antigens from other pathogens and thus form the basis of a range of multi-valent vaccines.

Vaccines containing bacteria attenuated by mutations in two genes of the

Vaccines containing a salmonella bacteria attenuated by mutation of the

An attenuated microorganism harbouring two mutated genes, each of which is located in the organisms aromatic pathway is provided. These organisms can usefully form the basis of a vaccine. They can be genetically engineered so as to express antigens from other pathogens and thus form the basis of a range of multi-valent vaccines.

Vaccines containing salmonella bacteria attenuated by mutations in two

The invention concerns a method of prophylactically treating a host against infection by a microorganism, which method comprises administering to the host an attenuated Salmonella bacterium which contains a nirB promoter operably linked to a DNA sequence encoding a heterologous protein. The heterologous protein is expressed in the host and induces in the host an immune response against the microorganism.

Expression of recombinant proteins in attenuated bacteria

The invention concerns a vaccine comprising an attenuated Salmonella bacterium which contains a nirB promoter operably linked to a DNA sequence encoding a heterologous protein. The nirB promoter directs expression of the heterologous protein in a host it is wished to vaccinate.

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Beckenham, United Kingdom

Steven Neville Chatfield