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Contenu archivé le 2024-04-16

Improvement of brucellosis prevention : development of a vaccine and a serologic test using different recombinant antigens to discriminate vaccinated from infected animals

Objectif

Brucellosis, a worldwide zoonosis causing abortion in cattle, sheep and goats, raises great concern not only because of possible human contamination but also because of economic losses. Eradication of the disease was achieved, only in some countries, by using a two step procedure: 4 to 5 years of vaccination to reduce the occurrence of the disease and when the serological response due to vaccination becomes negligible, slaughtering of serologically positive animals.

The final goal of the project is the development of a new vaccine and a diagnostic test using different recombinant antigens to enable the distinction between vaccinated and infected animals. These original tools will speed up the eradication of brucellosis in sheep and goats and avoid important economic losses to the Community and the farmers.
The aim of this research project has been the development of a new vaccine based on the knowledge of the pathogenesis of the Brucellosis bacteria and on the new technologies in the field of molecular genetics and immunology. Simultaneously, a diagnostic tool is being developed that will allow the differential diagnosis between animals treated with the new developed vaccine and infected animals.To acheive these goals Brucella protein antigens have been produced by recombinanat DNA techniques and their performance in serology has been evaluated. In parallel,presently available vaccine strains have been deleted in the genes encoding these diagnostic important proteins to avoid seroconversion upon vaccination. The strains have been studied in the mouse model to determine the residual virulence and to evaluate the protective effect upon challenge with a virulent Brucella strain. These experiments have yield encouraging results which warrent the furthur exploration of this vaccination and serology coupled system in a target animal like sheep or goats.
The vaccine will be based on a cell wall fraction of smooth brucella, already shown to be protective in a mouse model.

Suitable diagnostic antigens will be selected from a cytoplasmic protein and some minor outer membrane proteins. An enzyme linked immunosorbant assay, using the most suitable antigens, will be developed. The work proposed will lead to the conception of new prophylactic tools to speed up the eradication of brucellosis. The number of animals to be killed will be considerably decreased avoiding important economical losses in the Community. In Europe about 100 million animals have to be controlled and protected every year, and a successful vaccination programme will probably be the best way to prevent disease dissemination in all the countries after opening of the market in 1992. However the diagnostic assays will have to be able to differentiate vaccinated from infected animals. The scientific approach followed for this research will be transposable to other infectious diseases.

Recombinant vaccinal bacteria or hybridomas will be less hazardous and easier to cultivate than the attenuated brucella vaccine currently used. Better levels of brucellosis control is expected as the use and interpretation of the new vaccinal and diagnostic antigens will be cheaper and easier to use with the concurrent reduction in production and control costs.

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