Targeting cattle-borne zoonoses and cattle pathogens using a novel trypanosomatid-based delivery system

Area of Science:

• Veterinary Parasitology
• Molecular Biology
• Vaccine Development

Background:

• Trypanosomatid parasites cause significant diseases in humans and animals globally.
• Non-pathogenic trypanosomatids, like Trypanosoma (Megatrypanum) theileri, are globally distributed commensals of bovids.
• Existing knowledge of pathogenic trypanosomatids can be leveraged for novel applications.

Purpose of the Study:

• To develop Trypanosoma theileri as a novel vehicle for delivering vaccine antigens and proteins to cattle.
• To optimize conditions for the growth and transfection of T. theileri for protein expression.
• To evaluate the in vivo efficacy of engineered T. theileri in generating protective immune responses in cattle.

Main Methods:

• Optimized growth and transfection protocols for Trypanosoma theileri.
• Engineered T. theileri to express heterologous proteins using Trypanosoma brucei trafficking signals.
• Administered engineered T. theileri to cattle and assessed its persistence and immunogenicity.

Main Results:

• Engineered T. theileri successfully established and was maintained long-term in cattle, even with pre-existing natural populations.
• The engineered vehicle generated specific immune responses to an expressed Babesia antigen at protective levels.
• Demonstrated potential for T. theileri to deliver antigens for protection against Babesia and other cattle-borne zoonoses.

Conclusions:

• Trypanosoma theileri is a viable and effective novel vehicle for vaccine antigen delivery in cattle.
• This platform offers potential for developing vaccines against major cattle diseases and zoonoses.
• The approach could significantly impact livestock health and alleviate poverty by protecting cattle from diseases like African trypanosomiasis.