Desarrollo de vacunas frente a la neosporosis bovina utilizando aislados de "Neospora caninum" inactivados y atenuados

Résumé

Neospora caninum is an intracellular cyst-forming parasite known as a major cause of bovine abortion worldwide. Due to the negative economic impact of bovine neosporosis, together with the lack of cost-effective measures for its control, the development of an economically viable, efficacious and safe vaccine against abortion and parasite transmission has become one of the main challenges for the research of this disease. In the last few years, many studies have been carried out with the aim of developing vaccines against bovine neosporosis, including live, inactivated, and new generation protein recombinant, live vector or DNA vaccines. Up to now, new generation vaccines offer an interesting potential for the future, but have shown insufficient protection results. Contrarily, inactivated and live attenuated vaccines are the only ones that have been tested in bovine models with some success so far. This fact motivated the present Doctoral Thesis. The first part of the study evaluated the protection conferred by vaccines containing nactivated whole parasites as antigen. In these types of formulations, an appropriate selection of certain variables, such as the type of antigen or the adjuvant, may determine the induction of a protective immune response against N. caninum infection. Therefore, the first experiment examined the role of three different adjuvants (water-in-oil emulsion -W/O- and aluminum hydroxide plus CpG-ODN -Al/CpG- or plus ginseng extract -Al/G) combined with three different doses of whole inactivated tachyzoites (105, 5×105 and 106) using a mouse model of cerebral neosporosis (Chapter I). The results highlighted the influence of the adjuvant on the protective efficacy of the vaccine. Thus, immunization with W/O combined with 5×105 tachyzoites limited parasite presence in the brain during the chronic stage of the infection and, consequently, the possibility that the infection becomes chronic and persistent in this organ. Contrarily, Al/G plus 5×105 tachyzoites reduced parasitaemia during the acute stage of the infection. The antigen dose played a role in the protective efficacy of the vaccine, although it was less significant than the adjuvant’s: among the groups immunized with Al/G, parasite frequency and load in the brain rised as the dose was increased.