Intranasal vaccination against cutaneous leishmaniasis with a particulated leishmanial antigen or DNA encoding LACK.
We have previously demonstrated that oral delivery of a disease-promoting particulated antigen of Leishmania amazonensis (LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 microg of LaAg and were challenged 1 week postvaccination with L. amazonensis developed delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-gamma) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 microg/dose) had no effect. Interestingly, LACK DNA (30 microg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-gamma. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil.
Eduardo Fonseca
EF
Pinto
Roberta Olmo
RO
Pinheiro
Alice
A
Rayol
Vicente
V
Larraga
Bartira
B
Rossi-Bergmann
D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016054:DNA, Protozoan / Q000008:administration & dosage / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007891:Leishmania / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012995:Solubility; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination
D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D016753:Interleukin-10; C093139:LACK antigen, Leishmania; D007371:Interferon-gamma