Efficacy of vaccination with a combination of Leishmania amastigote antigens and the lipid A-analogue ONO-4007 for immunoprophylaxis and immunotherapy against Leishmania amazonensis infection in a murine model of New World cutaneous leishmaniasis.
Activation of innate immunity using adjuvants that activate Toll-like receptor 4 pathways have great potential for improving the protection induced by parasite vaccines. We investigated protective and therapeutic effects of a vaccine against leishmaniasis containing a combination of an adjuvant synthetic lipid A-analogue, ONO-4007 and Leishmania amazonensis antigens. ONO-4007 was co-injected with soluble and membrane-enriched L. amazonensis-amastigote antigens into BALB/c mice that had either already been infected with 1 x 10(6) L. amazonensis promastigotes (immunotherapy study) or before challenge with the same infectious dose (immunoprophylaxis study). Sixty percent of mice vaccinated before infectious challenge controlled their Leishmania infections - defined by the absence of footpad-swelling and negative Leishmania cultures - compared to 0% of controls, and 40% of mice vaccinated after infection resolved their infections compared to 0% of controls. Protective immunity in both immunoprophylaxis and immunotherapy models was associated with increased protein production of IL-12 and IFN-gamma. These data suggest that vaccination with a combination of ONO-4007 and amastigote antigens of L. amazonensis may be useful for the prevention and treatment of leishmaniasis, and that the protective immunity induced is associated with the production of type-1 cytokines.
Calvopina
Manuel
M
Department of Parasitology, Kochi Medical School, Kochi University, Kochi 783-8505, Japan. mcalvopina@hotmail.com
Barroso
Paola A
PA
Marco
Jorge D
JD
Korenaga
Masataka
M
Cooper
Philip J
PJ
Nonaka
Shigeo
S
Hashiguchi
Yoshihisa
Y
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007891:Leishmania / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000953:Antigens, Protozoan; D008050:Lipid A; C086889:ONO 4007; D016052:Protozoan Vaccines; D018664:Interleukin-12; D007371:Interferon-gamma