Further analysis of protection induced by the MIC3 DNA vaccine against T. gondii: CD4 and CD8 T cells are the major effectors of the MIC3 DNA vaccine-induced protection, both Lectin-like and EGF-like domains of MIC3 conferred protection.
The present study was conducted mainly to evaluate the contribution of the cellular and the humoral responses in protection conferred by the MIC3 DNA vaccine (pMIC3i) that was proved as a potent vaccine against toxoplasmosis. We performed the adoptive transfer of CD4(+) and CD8(+) T lymphocytes from pMIC3i immunized mice to naive ones and the role of humoral immunity was evaluated by in vitro invasion assays. We also constructed plasmids encoding the EGF-like domains and the Lectin-like domain of MIC3, to define which domains of MIC3 are involved in the protection. Furthermore, the adjuvant effect of the GM-CSF-expressing vector (granulocyte-macrophage colony-stimulating factor) required the precise temporal and spatial codelivery of GM-CSF with antigen, thus, we constructed a bicistronic plasmid expressing MIC3 and GM-CSF. In conclusion, the protection induced by pMIC3i was mainly mediated by CD4(+) and CD8(+) T lymphocytes and both EGF and Lectin domains of MIC3 conferred protection. Furthermore, the codelivery of GM-CSF by a bicistronic plasmid appeared to be a most effective way for enhancing the adjuvant properties of GM-CSF.
Université François Rabelais, INRA, UMR 0483 Université-INRA d'Immunologie Parasitaire, Vaccinologie et Biothérapies Anti-Infectieuses, IFR 136 Agents transmissibles et Infectiologie, UFR des Sciences Pharmaceutiques, Tours, France.
Alaa Bassuny
AB
Ismael
Dorsaf
D
Hedhli
Odile
O
Cérède
Maryse
M
Lebrun
Isabelle
I
Dimier-Poisson
Marie-Noëlle
MN
Mévélec
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001921:Brain / Q000469:parasitology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D009500:Neutralization Tests; D010957:Plasmids; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014123:Toxoplasmosis / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; C421382:MIC3 protein, Toxoplasma gondii; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor