Location: Animal Disease Research
Project Number: 2090-32000-039-008-A
Project Type: Cooperative Agreement
Start Date: Oct 1, 2014
End Date: Sep 30, 2019
Objective:
Test the hypothesis that delivery of T. parva schizont antigens via a Bovine Herpes Virus-4 (BHV-4) platform induces parasite-specific immune responses in cattle that prevent morbidity and mortality. Specific objectives proposed to test this hypothesis are: (1) determine the functional activity and duration of immune responses to T. parva induced by recombinant BHV-4 immunization; and (2) test the ability of immunized cattle to resist T. parva challenge.
Approach:
Objective 1: Detailed investigation of the immune responses induced by recombinant BHV-4 viruses expressing Tp2 and Tp9 will be conducted in ten calves of defined MHC types. Immune responses will be monitored over a period of four weeks following immunization. Animals expressing Class I A10 or A14 (known to generate CD4 and CD8 T cell responses to Tp2 and Tp9) in combination with other defined Class I MHC haplotypes will be used. The use of these genotypes provides animals that are predicted to generate strong responses to defined Tp2 and Tp9 epitopes (A10 and A14 respectively), and will also allow induction of responses restricted by the other MHC haplotypes to be detected.
Objective 2: To achieve this objective, ten calves vaccinated with the recombinant BHV-4 viruses (expressing Tp2 and separately Tp9), as described in Objective 1, will be challenged with a lethal dose of T. parva sporozoites. The clinical reactions and kinetics of parasite development will be compared in the vaccinated animals and the kinetics of recall of CD4 and CD8 T cell responses specific for Tp2 and Tp9 will be monitored following challenge in the vaccinated animals.
Challenge groups will include five non-vaccinated cattle and five cattle vaccinated with native BHV-4.
