Rosenberg, Carina Agerbo2; De Craeye, S.3; Jongert, E.3; Gargano, N.3; Beghetto, E.3; Del Porto, P.3; Vorup-Jensen, Thomas6; Petersen, Jørgen Eskild7
1 The Department of Infectious Diseases, Faculty of Health Sciences, Aarhus University, Aarhus University2 Department of Medical Microbiology and Immunology, Faculty of Health Sciences, Aarhus University, Aarhus University3 unknown4 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University5 Department of Clinical Medicine - Department of Infectious Diseases, Department of Clinical Medicine, Health, Aarhus University6 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University7 Department of Clinical Medicine - Department of Infectious Diseases, Department of Clinical Medicine, Health, Aarhus University
Infection with the obligate intracellular parasite Toxoplasma gondii is a significant source of parasitic infections worldwide. In adults, infections may often lead to severe retinochoroiditis. Infection of the foetus causes abortion or congenital pathology that may lead to neurological complications. Although several strategies have been suggested for making a vaccine, none is currently available. Here, we investigate the protection conferred by DNA vaccination with two constructs, pcEC2 (MIC2-MIC3-SAG1) and pcEC3 (GRA3-GRA7-M2AP), encoding chimeric proteins containing multiple antigenic sequences from T. gondii. After challenge with a T. gondii genotype II, but not a genotype III strain, a significant decrease in cerebral cyst load was found compared to the controls. The immune protection involved a cell-mediated immune response with the synthesis of the cytokines IFN-? and IL-10. In silico structure analysis and the expression profile of EC2, suggest an association between antigen stability, the degree of protein secondary structure and induction of cellular immune responses. Intracellular protein degradation is an important step in the pathway leading to presentation of antigenic peptides on Major Histocompatibility Complex molecules. We suggest that degradation of this chimeric protein may have contributed to the induction of a cellular immune response via enhanced presentation of antigenic peptides on Major Histocompatibility Complex class I molecules.