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Generation of Vaccine Candidates Against Mycobacterium bovis - SE3208

The current test and slaughter policy used for the control of Mycobacterium bovis infection in cattle has failed to prevent a sharp rise in cases of bovine tuberculosis in recent years, especially in the south-west of England. The recently published Krebs Report [1] on bovine tuberculosis in cattle and badgers has recommended that the best prospect for control in the British herd is to develop a cattle vaccine. The Report also recommended that the option of a badger vaccine should be retained. The aim of this proposal is to apply recent advances in mycobacterial genetics and vaccinology to the development of vaccine candidates and will build on advances already made as a result of MAFF ROAME funding at VLA aimed at the development of a badger vaccine. Live vaccine candidates will be generated by transposon mutagenesis and rational attenuation of GB strains of M. bovis. Live vaccines will also be generated at AgResearch, Wallaceville, NZ, by illegitimate recombination. Subunit vaccines will be generated by the production of DNA vaccines using genes encoding immunodominant antigens identified by screening M. bovis cosmid libraries against blood from M. bovis-infected cattle. Promising vaccine candidates will also be obtained from collaborating laboratories and via the Animal Models Task force of IMMYC. The efficacy of these candidates will be assessed in small animal models and cattle as part of a co-ordinated programme of vaccine development at VLA (proposals XF0304, XF0311 and XF0314).
Obj. No. Completed by date Description

To compare M. bovis genome sequence of strain 2212/97 with that of M. tuberculosis H37Rv and M. tuberculosis CSU#93 and BCG and target differences to generate candidate vaccines.

To characterise fully a mutant library of M. bovis generated by transposon mutagenesis and to select mutants from this library for testing as vaccine candidates.

To produce 2,000 illegitimate recombinants of M. bovis and to identify suitable vaccine candidates from these mutants.

To produce rationally attenuated vaccines lacking genes that are upregulated in vivo.

To remove antigens immunodominant in cattle from M. bovis vaccine strain by homologous recombination. The immunodominant antigens will be used for diagnosis. This will facilitate differential diagnosis between animals infected with M. bovis and those vaccinated with the live, attenuated vaccine.

To produce new and improved naked DNA constructs encoding antigens which are immunodominant in cattle.

To co-ordinate human and bovine TB vaccine development via the Animal Model Task Force of IMMYC.

To continue links with Veterinary Industrial Partners (including Hoechst Roussell Vet) so that vaccine candidates which can be produced cost-effectively and delivered into the field can be identified at an early stage of development.

Project Documents
• Final Report : Generation of vaccine candidates against M. bovis   (909k)
Time-Scale and Cost
From: 1999

To: 2005

Cost: £1,566,005
Contractor / Funded Organisations
Veterinary Laboratories Agency
Animal Health              
Bovine Tuberculosis              
Genetically modified food and crops              
GM Non-Food              
Plants and Animals              
Fields of Study
Animal Health