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Peripheral expression of LACK-mRNA induced by intranasal vaccination with PCI-NEO-LACK defines the protection duration against murine visceral leishmaniasis

Published online by Cambridge University Press:  19 July 2012

DANIEL CLÁUDIO DE OLIVEIRA GOMES ,
RODRIGO PORTO SCHWEDERSKY ,
LUIZ DIONE BARBOSA DE-MELO ,
BEATRIZ LILIAN DA SILVA COSTA SOUZA ,
HERBERT LEONEL DE MATOS GUEDES ,
ULISSES GAZOS LOPES  and
BARTIRA ROSSI-BERGMANN
DANIEL CLÁUDIO DE OLIVEIRA GOMES*
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil Laboratório de Imunologia Celular e Molecular, Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, 29040-091, Vitória, ES, Brazil
RODRIGO PORTO SCHWEDERSKY
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
LUIZ DIONE BARBOSA DE-MELO
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil Laboratório de Genética Molecular, Instituto Federal de Educação Ciência e Tecnologia do Rio de Janeiro, 20270-021, Rio de Janeiro, RJ, Brazil
BEATRIZ LILIAN DA SILVA COSTA SOUZA
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
HERBERT LEONEL DE MATOS GUEDES
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
ULISSES GAZOS LOPES
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
BARTIRA ROSSI-BERGMANN
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil
*
*Corresponding author: Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil. Tel/Fax: +55 27 3335 7210 and +55 27 3335 7268. E-mail: dgomes@ndi.ufes.br
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Summary

LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in the protozoan of the genus Leishmania, which is associated with the immunopathogenesis and susceptibility of BALB/c mice to Leishmania major infection. We previously demonstrated that intranasal immunization with a plasmid DNA encoding the p36/LACK leishmanial antigen (pCI-neo-LACK) followed by challenge 7 days after a booster dose effectively protects BALB/c mice against both cutaneous and visceral leishmaniasis. In the present study, the correlation between systemic mRNA expression after nasal DNA uptake, and the duration of protective immunity was addressed. LACK mRNA transcripts were detected in the spleen, brain, cervical lymph nodes and popliteal lymph nodes as early as 7 days, lasting 3 months after vaccination with pCI-neo-LACK. The kinetics of transcript expression correlated with enhanced cutaneous hypersensitivity against parasite antigens. Leishmania chagasi infection at 7 days or 3 months, but not 6 months after vaccination resulted in significantly lower parasite loads as compared with non-vaccinated controls. Protection also correlated with enhanced spleen cell responsiveness to parasite antigens leading to increased IFN- γ and IL-4 and decreased IL-10 production. Together, these data demonstrate that the protection conferred by the intranasal DNA vaccine lasts at least 3 months and is associated with expression of vaccine mRNA in peripheral organs.

Keywords

leishmaniasisLeishmania chagasiintranasalDNA-vaccineLACK
Type
Research Article
Information
Parasitology , Volume 139 , Issue 12 , October 2012 , pp. 1562 - 1569
Copyright
Copyright © Cambridge University Press 2012

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