Induction of a Th1 immune response and simultaneous lack of activation of a Th2 response are required for generation of immunity to leishmaniasis.
Experimental systems based on immunization with plasmid DNA or immune-stimulating complexes were used to delineate the requirements for generation of protective immunity against murine leishmaniasis. Vaccination with plasmid DNA encoding the host-protective Leishmania major parasite surface Ag-2 primed for an essentially exclusive Th1 response that protected mice against L. major infection. In contrast, parasite surface Ag-2 in immune-stimulating complexes generated an immune response with mixed Th1-like and Th2-like properties that was not protective despite the activation of large numbers of CD4+ T cells secreting IFN-gamma. These results indicate that a Th1 response is sufficient to protect against cutaneous leishmaniasis, but the induction of a simultaneous Th2 response abrogates the Th1 effector function. DNA vaccines may therefore have an advantage for diseases in which protection depends on the induction of Th1 responses.
Sjölander
A
A
The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia.
Baldwin
T M
TM
Curtis
J M
JM
Handman
E
E
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D016054:DNA, Protozoan / Q000235:genetics; D005260:Female; D016882:ISCOMs / Q000494:pharmacology; D007074:Immunoglobulin G / Q000096:biosynthesis; D018320:Leishmania major / Q000235:genetics; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D015800:Protozoan Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000494:pharmacology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016207:Cytokines; D016054:DNA, Protozoan; D016882:ISCOMs; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C072094:surface antigen P2, Leishmania