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EC INCO-DEV PROGRAMME

International Cooperation with Developing Countries

Development of recombinant BCG multivaccine for predominant parasitic and epizootic disease of ruminants in Latin America

Project Summary
Infectious diseases are the cause of a major cause of loss to the livestock industry world-wide but particularly in the developing world. Current control measures are often ineffective or too expensive for small farmers. We aim to develop a novel vaccine, based on the BCG vaccine, for control of the predominant parasitic diseases that afflict domestic ruminants in Latin America. The BCG vaccine is one of the most widely used vaccines in the world; it can be administered at birth and a single dose delivers long-lasting immunity. It is cheap to produce and is one of the most heat-stable of vaccines. It is therefore ideally suited to the problems of disease control in the developing world. Our objective is to clone antigens from the predominant ruminant parasitic diseases caused by Fasciola hepatica, anaplasma and babesia, into BCG to develop a recombinant BCG (rBCG) multivaccine capable of conferring immunity, not only to tuberculosis (TB), but also against the target parasitic diseases. Such a vaccine would have the potential to significantly reduce losses for farmers, particularly small-scale farmers in developing countries.
Although the BCG vaccine is derived from a bovine strain of the tubercle bacillus (Mycobacterium bovis), it has not been widely used in ruminants because of interference with the tuberculin test for diagnosis of TB. To circumvent this problem we will develop our rBCG vaccine in a genetically modified strain of BCG that is inactivated for expression of immunodominant M. bovis proteins. This will allow us to develop, in parallel with the vaccine, a diagnostic test that targets the proteins inactivated in our vaccine strain (but present in wild-type M. bovis). The proposed immunodiagnostic test will react positively with tuberculous-infected animals and may therefore be used for control of TB in cattle. However, in contrast to the tuberculin test, it will not react with rBCG-vaccinated animals. The combination of rBCG multivaccine and compatible diagnostic for TB will allow affordable control of ruminant disease in developing countries. The project represents a partnership between laboratories in the EU and in Latin America with complementary expertise in mycobacterial genetics, vaccinology, parasitology and veterinary research. Both end-user and commercial interests are represented in the partnership in order to ensure that the deliverables of this project (new vaccines, new diagnostics) are appropriately developed for optimal application in the target countries.

Work plan
The Work plan is divided into four interrelated Workpackages:

Work
package
Work package title Lead
contractor
1 Development of BCG/TB immunodiagnostic test system to distinguish between vaccination and natural infection. Dr Marian Kane
2 Development of BCG/vector systems for optimal delivery of foreign antigens to bovine cells Dr Luciana leite
3 Generation and testing of rBCG strains expressing antigens from babesia, anaplasma and helminths. Dr Angel Cataldi
4 Immunogenicity and protective efficacy of candidate rBCG vaccines in ruminants Dr Miriam Tendler