Development of a recombinant parapoxvirus vaccine to protect against Toxoplasma gondii infection in sheep
Live virus vaccines are excellent inducers of long-term immunity by eliciting protective humoral and cell-mediated immune responses against foreign antigens. To this end, recombinant poxviruses are one of the most versatile expression systems for foreign antigens and have been extensively developed as vaccine vectors for veterinary diseases. Recently, the type species ORFV (ORFV) of the genus Parapoxvirus in the family Poxviridae has been investigated as a novel vaccine vector. Attributes that favor the use of ORFV as a vaccine vector include: limited host range (sheep and goats), restricted tropism to the skin, lack of systemic infection, short-term vector-specific protective immunity, and unique immune-modulating properties which strongly stimulate the innate immune response at the site of infection, induce a potent Th1 immune response and rapidly generate foreign antigen-specific immune responses. Due to the large genome size of ORFV, it is possible to insert multiple antigens thereby producing multivalent vaccines.
Toxoplasmosis is a disease caused by the parasite Toxoplasma gondii (T. gondii) and is one of the most common parasitic diseases of warm-blooded animals. In humans, T.gondii infection can cause severe disease in immunocompromised individuals and pregnant women and latent Toxoplasma infections have been associated with behavioural changes and schizophrenia. T. gondii is also the most common cause of infectious abortion in sheep and goats in Ontario. Studies have indicated that there is widespread environmental contamination with T. gondii oocysts and producers in Canada have no means of controlling infection. The objective of this research project is to develop a recombinant parapoxvirus vaccine expressing three different T. gondii protective antigens (SAG1-ROP2-GRA2) and to evaluate the immunogenicity and protective efficacy of the rORFV/SAG1-ROP2-GRA2 vaccine in mice and sheep. We anticipate that sheep immunized with rORFV-SAG1-ROP2-GRA2 will develop a robust immune response against T. gondii that will lead to a reduction in tissue cyst formation and ultimately, protection against congenital infection.
Collaborators:
- Dr. Karen Shapiro, University of California Davis, University of Guelph
- Dr. Paula Menzies, Ontario Veterinary College
- Dr. Byram Bridle, University of Guelph
