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Contenuto archiviato il 2024-04-30

Development of a genetically modified brucella melitensis rev1 live vaccine and associated diagnostic assay allowing discrimination between vaccinated and infected sheep

Obiettivo

Brucellosis in small ruminants caused by Brucella melitensis is the most widespread form of animal brucellosis in the mediterranean countries of the European Union (EU). The main problem is due to sheep brucellosis which is responsible for important economic losses through interference with breeding programmes and reduction in milk yield, and also constitutes a serious hazard to public health as B. melitensis is very pathogenic for humans. In the same regions, the ram contagious epididymitis caused by Brucella ovis is also a disease of economical importance. In the southern Europe where sheep brucellosis is endemic, efforts are still to be made to reduce the prevalence to a level at which the elimination of infected animals is economically feasible. At this stage, vaccination is the only suitable method for controlling the infection in animals and thus constitutes a real priority. B. melitensis strain Rev. 1 is worldwide accepted as the reference live vaccine against B. melitensis or B. ovis infection in sheep. Rev. 1 has however a serious side effect due to its interference with the serological diagnosis of the field infection. This interference does not allow discrimination between vaccinated and infected animals, thus making sanitary management more difficult to achieve.

Therefore, the development of an effective live vaccine devoid of this disadvantage is highly desirable and justified. The objective of this project is therefore to develop a stable vaccinal strain of B. melifensis Rev. 1 devoid of specific diagnostic proteins by gene replacement technology which, by virtue of lacking genes encoding these proteins, would induce protection but would not induce antibody response against the missing proteins. The use of these antigens, produced as recombinant proteins, in new diagnostic tests based on humoral or cellular immunity, would allow to discriminate vaccinated from infected animals. The critical point for the success of the project is to carefully select the antigens, the genes of which will be deleted from the genome of the vaccinal strain. These antigens should indeed be the best of all possible diagnostic antigens, i.e. they should detect most if not all infected animals and provide negative results with vaccinated and Brucella-free animals. Recent work on Brucella protein antigens has led to the conclusion that both the periplasmic protein of 26 kDa (BP26) and the outer membrane protein of 31 kDa (Omp3 1) are suitable antigens for the diagnosis of brucellosis in sheep, and that they should facilitate the development of sensitive and specific immunological tests using mixtures of recombinant proteins. Because of their good diagnostic value, the BP26 and Omp3 1 antigens have been selected in this project for developing, by gene replacement technology, genetically modified Rev. 1 strains deleted in one or both genes. The engineered Rev.1 strains will be evaluated for residual virulence, protective capacity and compatibility with the new diagnostic tests, both in mice and sheep models. The project builds upon the more recent results, gained during the two last years, on Brucella diagnostic antigens.

It should ultimately lead to the development of a diagnostically distinguishable engineered B. melifensis Rev. 1 vaccinal strain that would hasten the eradication of this zoonotic disease from the EU and the achievement of a uniform animal health status throughout the Union. This would also promote the control of the animal source of human pathogens.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.

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Coordinatore

INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHES DE TOURS
Contributo UE
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Indirizzo

37380 NOUZILLY
Francia

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