title: Peripheral expression of LACK-mRNA induced by intranasal vaccination with PCI-NEO-LACK defines the protection duration against murine visceral leishmaniasis.
abstract: 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.
authors.affiliation: Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil. dgomes@ndi.ufes.br
authors.forename: Daniel Cláudio
authors.initials: DC
authors.lastname: De Oliveira Gomes
authors.forename: Rodrigo Porto
authors.initials: RP
authors.lastname: Schwedersky
authors.forename: Luiz Dione
authors.initials: LD
authors.lastname: Barbosa De-Melo
authors.forename: Beatriz Lilian
authors.initials: BL
authors.lastname: Da Silva Costa Souza
authors.forename: Herbert Leonel
authors.initials: HL
authors.lastname: De Matos Guedes
authors.forename: Ulisses Gazos
authors.initials: UG
authors.lastname: Lopes
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012333:RNA, Messenger / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D012333:RNA, Messenger; C093139:LACK antigen, Leishmania