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Objectives

Management of ticks and tick-borne disease (TTBDS) is primarily through the control of the tick vector using acaricides, although this is unsustainable due to increasing acaricide resistance and food safety concems. In some endemic regions, attenuated live vaccines have been developed for bovine piroplasmosis (Theileria and Babesia) however, there has been limited development of vaccines for small ruminant piroplasmosis.

Consequently, the PiroVac project was developed as an integrated approach, encompassing immunology, molecular biology, bioinformatics and genetic engineering together with pathogen genomics and host genetics which is directed at addressing two broad aims:

  1. Development of effective and reliable vaccines for use in disease control campaigns for sustainable livestock development.

  2. Capacity-building for the sustainable implementation of integrated control measures required for disease control and/or eradication through increasing scientific knowledge, training and improvement of infrastructure.

PiroVac will exploit technology to improve the existing T. lestoquardi vaccine and design new vaccines focusing on malignant theileriosis and babesiosis in small ruminants. A wealth of scientific information will be generated that will facilitate the upgrading of production systems using more productive, but disease-susceptible, breeds for improving the genetics of local flocks. The overall objective of the project is to ensure food security and to improve food safety by improving control measures for small ruminant piroplasmosis caused by T. lestoquardi, T. uilenbergi and B. ovis. To achieve these goals the project will assess parasite diversity and identify molecules associated with attenuation of parasite virulence to be included in the development of safe and efficacious live vaccines. For the improvement of the attenuated T. lestoquardi vaccine, a combination of the existing vaccine with sub-unit vaccines will be examined for synergistic effects. Also, by improving the vaccine shelf-life and storage conditions, it is hoped there will be a decreased requirement for a 'cold chain'. The specific goals of the project are:


1. Improvement and development of live attenuated vaccines for the control of small ruminant theileriosis and babesiosis through determining the effectiveness of attenuation using:

a. in vivo assessment of attenuation, analysing clinical and immunological criteria (both humoral and cellular responses) of immunised and challenged animals

b. subtractive libraries and microarray analysis for the identification of attenuation markers

 

2. Sub-unit vaccine design through:

a. identification of suitable antigens using a combination of genomics, bioinformatics and gene expression analysis coupled with experimental confirmation of antigen localisation and presentation. To facilitate antigen discovery, parasite molecules involved in host cell invasion, activation of cytokine-producing CD4+ T cells and NK cells and activation of cytotoxic T-lymphocytes involved in killing of T. lestoquardi-infected leucocytes will be identified.

b. immunological characterisation of the identified antigens as potential vaccine candidates.

3. Vaccination trials using:

a. live attenuated vaccines

b. recombinant protein and DNA vaccines


More broadly, the project will contribute to an understanding of the immunological and molecular mechanisms involved in host-pathogen interaction. As important by-products of the project, reagents required for the characterisation of the innate and adaptive immunity of small ruminants will be generated together with the genome sequences of the three pathogens under study.

The PiroVac project is based on the conviction that the interface between genomics, immunology and vaccinology offers the best prospect for major breakthroughs in vaccine discovery and development. Overall, vaccine development will contribute to reducing losses in animal production due to piroplasmosis of small ruminants and improve the life quality of both farmers and consumers.

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