Optimization of DNA vaccination against cutaneous leishmaniasis.
The present studies were designed to examine the requirements of dose, route of inoculation and constituent antigens for the maintenance of complete and long lasting protection against cutaneous leishmaniasis due to Leishmania major conferred by a cocktail DNA vaccine encoding the Leishmania antigens LACK, LmST11 and TSA. Vaccination of C57Bl/6 mice with LACK DNA alone resulted in partial protection, whereas the combination of LmST11 and TSA provided stronger, though still incomplete protection compared to the combination of all three Ag DNAs. When intradermal (i.d), intramuscular (i.m.), and subcutaneous (s.c.) vaccination routes were compared, i.d. immunization reduced by five-fold the dose necessary to maintain complete protection. In vivo depletion of CD4+ or CD8+ T cells provided direct evidence that both populations are necessary to mediate complete protection. These results establish intradermal vaccination using DNA encoding multiple Leishmania antigens as a way to optimize priming of CD4+ and CD8+ T cells necessary for potent and durable protection against cutaneous leishmaniasis.
Méndez
Susana
S
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 126, Building 4, Center Dr MSC 0425, Bethesda, MD 20892-0425, USA.
Belkaid
Yasmine
Y
Seder
Robert A
RA
Sacks
David
D
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000953:Antigens, Protozoan / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016054:DNA, Protozoan / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D004333:Drug Administration Routes; D007111:Immunity, Cellular / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D018320:Leishmania major / Q000276:immunology* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000473:pathology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000627:therapeutic use*; D015164:Vaccines, Inactivated / Q000627:therapeutic use
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated