Induction of partial protection against infection with Toxoplasma gondii genotype II by DNA vaccination with recombinant chimeric tachyzoite antigens.
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.
Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.
Carina
C
Rosenberg
Stéphane
S
De Craeye
Erik
E
Jongert
Nicola
N
Gargano
Elisa
E
Beghetto
Paola
P
Del Porto
Thomas
T
Vorup-Jensen
Eskild
E
Petersen
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005838:Genotype; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014122:Toxoplasma / Q000145:classification / Q000235:genetics / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000517:prevention & control; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D016052:Protozoan Vaccines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA