971516A novel livestock vaccination platform to prevent zoonotic emerging infectionsClosedSmall Business Research InitiativeInnovate UKTITLE: A novel livestock vaccination platform to prevent zoonotic emerging infections Emerging and epidemic infections are frequently passed to humans through their interactions with livestock. Examples include infection with Coxiella burnetii (causing Q fever), Rift Valley Fever virus (RVFV) and Crimean Congo Haemorrhagic fever (CCHF) virus, each of which is sustained and sometimes amplified in animals. One approach to limit the risk of transmission is to vaccinate animals against infection, but this often involves the use of inactivated pathogens, which are expensive and difficult to produce and generate immune responses that are impossible to distinguish from natural infection. Vaccination can also be challenging in resource-poor settings, where effective veterinary management is lacking. Furthermore, emerging infections can evolve rapidly, such that the ability to reengineer or reformulate vaccines is necessary to retain their effectiveness. There is an urgent need for stable systems that can deliver multivalent antigens in cattle to limit human exposure. We have developed a novel, non-pathogenic protozoan parasite as a flexible and safe vaccine delivery vehicle that is well suited to deployment in low and middle income countries (LMIC). The parasite is the single-celled organism Trypanosoma theileri, which is found naturally in almost all cattle worldwide. This parasite can be easily and rapidly engineered to express heterologous antigens using existing modularised expression constructs that can be delivered systemically into recipients over a sustained period. Using an exemplar antigen from Babesia divergens (a cattle pathogen), we showed previously that vaccination using this system results in low-level prolonged immune stimulation to the delivered antigen at levels shown to generate protective immune responses to the target antigen. In the planned work, we will generate T. theileri lines expressing several antigens from the zoonotic threats, Coxiella, RVFV and CCHFV, and confirm their effective protein production using antibodies raised to recombinant proteins of each target. The vaccine vehicle will then be inoculated into cattle using T. theileri populations expressing one or more antigens (singly or in combination) and maintained over 12 weeks. Thereafter, immune responses generated to the expressed antigens will be measured to assess efficacy of immunisation in the context of single or multivalent delivery. We have shown previously that a single inoculation of the delivery vehicle is sufficient to establish and maintain persistence of the vehicle such that a ‘one-dose’ application suitable in LMIC is practical. The work here will demonstrate the potential for this flexible, sustained delivery system to protect cattle against emerging zoonotic infections, thus providing a barrier to epidemic outbreaks resulting from frequent human-animal contact in at-risk populations.