Optimization of the Theileria parva Antigen p67 for use in the Novel Bovine Herpesvirus-4 Vaccine Delivery Platform

Laura Williams

East Coast Fever (ECF), caused by the tick-borne protozoan parasite Theileria parva, results in significant bovine morbidity, mortality, and production losses in regions of sub-Saharan Africa. The development of a sustainable, deployable next-generation vaccine is critical to the long term control of ECF and improving the economics of the pastoral farmer. Herpesviruses as vaccine vector systems have been recently exploited due to their intrinsic ability to establish persistent infection, resulting in the provision of long-term antigen expression and antigen-specific immune responses. Bovine herpesvirus-4 (BoHV-4), a gammaherpesvirus, has inherent advantages as a vaccine platform for antigen delivery. Like other herpesviruses, BoHV-4 establishes a persistent infection, and may facilitate the long-term expression of T. parva antigens in the bovine host. BoHV-4 has shown clinical success in experimental vaccines against a variety of infectious diseases in multiple species by inducing high levels of serum-neutralizing antibodies to targeted pathogens. In this work, we provide evidence that recombinant bovine herpesvirus-4 is able to elicit robust antigen-specific neutralizing immunity following immunization of cattle via intranasal nebulization. More specifically, we show evidence that these responses can occur in the face of pre-existing BoHV-4 immunity. We also provide evidence that recombinant BoHV-4 persists in immunized cattle and that recrudescence of the virus boosts the immune response to BoHV-4-vectored antigens. Thus, BoHV-4 is considered an ideal vector for development of a next-generation vaccine against T. parva. The T. parva sporozoite surface antigen (p67) is known to generate anti-sporozoite antibody activity in cattle. Previous immunization studies have developed various forms of recombinant p67 capable of providing protection of cattle from severe ECF. However, optimization of p67 expression and p67-based immunization strategies is necessary. In this work, we describe the stable expression of full length, membrane-linked recombinant p67 in mammalian cells, which is immunogenic in cattle. The antigen expression system described here is expected to optimize p67-based immunization. The incorporation of the full-length p67 expression system developed in this study in the BoHV-4 vector system developed for cattle in this study is expected to optimize humoral antibody responses and provide clinical protection from disease in future vaccine development strategies.

Optimization of the Theileria parva Antigen p67 for use in the Novel Bovine Herpesvirus-4 Vaccine Delivery Platform

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