Toward a vaccine to prevent toxoplasmosis

The goal of our work will be to make a vaccine that protects against acquisition of infection with Toxplasma gondii, one of the most common parasitic pathogens in humans worldwide. For this purpose, we will determine optimal epitopes, which stimulate the protective immune response, using an immunosense approach and with epitope mapping of protective full-length proteins. We will include CD4 and CD8 T cell epitopes and B cell epitopes and full-length proteins that we have identified to date. We will also combine them with additional new epitopes. These new epitopes will be determined by their capability to induce interleukin-2 and interferon-gamma responses from CD4+ and CD8+ T cells from HLA-typed persons. We will determine optimal adjuvant and delivery systems for vaccines using epitope peptides, full length and fusion proteins, and DNA constructs, respectively. Our adjuvants will include bilosomes, GLA-SE (a TLR4 ligand), and electroporated DNA delivery. We will compare their efficiency as vaccine with that of a live attenuated organism vaccine. Challenge infection to evaluate the efficiency of the vaccines will be with tachyzoites, bradyzoites in cysts perorally, and sporozoites perorally. We will use the following parasite types for the challenge infection: types I, II, III, IV, VI, Brazilian and Guyana. We will utilize HLA supermotif-transgenic and humanized mice reconstituted with a human immune system for this evaluation. The evaluation will include the protection against acute and chronic infection, infection of the eye, and congenital infection. Our long-term objective is to create a vaccine that will protect humans against these infections. Each member of our consortium will contribute uniquely to this project with their own contributions to each phase of the work.