Failure of a vaccine using immunogenic recombinant proteins rNcSAG4 and rNcGRA7 against neosporosis in mice

Abstract

The development of an effective vaccine against Neospora caninum infection in cattle is an important issue due to the significant economic impact of this parasitic disease worldwide. In this work, the immune response, safety and efficacy of different vaccine formulations using the N. caninum recombinant proteins rNcSAG4 (the first bradyzoite-specific protein assayed as a vaccine) and rNcGRA7 were evaluated in mouse models. The survival curves of pups from all vaccinated groups showed a slight delay in time to death compared to control groups; this difference was statistically significant for rNcSAG4 + adjuvant group. Immune response of mice vaccinated with rNcSAG4 was characterized by reduced specific IgG and cytokine levels with an equilibrated IFN-gamma/IL-10 balance. Regarding mice vaccinated with rNcGRA7, a very strong humoral and cellular immune response was generated characterized by a hyper-production of IFN-gamma. This response was not accompanied by significant protection. Vaccination with a mixture of both recombinant proteins reduced infection in lung and brain during acute and chronic infection, respectively, although it was not statistically significant. In summary, no significant protection was obtained with these vaccine formulations in the present mouse models. However, the study reveals some positive results on immune response and efficacy for both recombinant proteins; these results are being discussed in order to suggest new approaches with new chronic infection mouse models and adjuvants.