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Infection and Immunity, August 2004, p. 4521-4527, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4521-4527.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

Eduardo Fonseca Pinto, Roberta Olmo Pinheiro,1 Alice Rayol,1 Vicente Larraga,2 and Bartira Rossi-Bergmann1*

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil,1 Centro de Investigaciones Biologicas, Madrid, Spain2

Received 10 March 2004/ Returned for modification 9 April 2004/ Accepted 2 May 2004

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 µg 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 µg/dose) had no effect. Interestingly, LACK DNA (30 µg/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.

* Corresponding author. Mailing address: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21.949-900 Rio de Janeiro-RJ, Brazil. Phone: 55 (21) 2260-6963. Fax: 55 (21) 2280-8193. E-mail: bartira{at}biof.ufrj.br.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2004, p. 4521-4527, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4521-4527.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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