title: Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice.
abstract: We have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as a more representative experimental model of human cutaneous leishmaniasis.
  
  
  
  C57BL/6 mice from different animal facilities were infected with L. amazonensis (Josefa strain) to establish the profile of infection. Intranasal vaccination was performed before the infection challenge with two doses of 10 μg of LaAg alone or associated with the adjuvant ADDAVAX® by instillation in the nostrils. The lesion progression was measured with a dial caliper and the parasite load by limited dilution assay in the acute and chronic phases of infection. Cytokines were quantified by ELISA in the homogenates of infected footpads.
  
  
  
  C57BL/6 mice from different animal facilities presented the same L. amazonensis infection profile, displaying a progressive acute phase followed by a controlled chronic phase. Parasites cultured in M199 and Schneider's media were equally infective. Intranasal vaccination with LaAg led to milder acute and chronic phases of the disease. The mechanism of protection was associated with increased production of IFN-gamma in the infected tissue as measured in the acute phase. Association with the ADDAVAX® adjuvant did not improve the efficacy of intranasal LaAg vaccination. Rather, ADDAVAX® reduced vaccination efficacy.
  
  
  
  This study demonstrates that the efficacy of adjuvant-free intranasal vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of infection with L. amazonensis, and is thus not exclusive to the susceptible BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to peripheral protection irrespective of the genetic background of the host.
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Juliana Elena Silveira
authors.initials: JE
authors.lastname: Pratti
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Tadeu Diniz
authors.initials: TD
authors.lastname: Ramos
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Joyce Carvalho
authors.initials: JC
authors.lastname: Pereira
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Alessandra Marcia
authors.initials: AM
authors.lastname: da Fonseca-Martins
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Diogo
authors.initials: D
authors.lastname: Maciel-Oliveira
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Oliveira-Silva
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Mirian França
authors.initials: MF
authors.lastname: de Mello
authors.affiliation: Laboratório Integrado de Imunoparasitologia, Campus Macaé-Universidade Federal do Rio de Janeiro, Macaé, Brazil.
authors.forename: Suzana Passos
authors.initials: SP
authors.lastname: Chaves
authors.affiliation: Laboratório de Imunobiologia, Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brazil.
authors.forename: Daniel Claudio Oliveira
authors.initials: DC
authors.lastname: Gomes
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Bruno Lourenço
authors.initials: BL
authors.lastname: Diaz
authors.affiliation: Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.affiliation: Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. herbert@biof.ufrj.br.|Núcleo Multidisciplinar de Pesquisa UFRJ-Xerém em Biologia (NUMPEX-BIO), Polo Avançado de Xerém-Universidade Federal do Rio de Janeiro, Duque de Caxias, Rio de Janeiro, Brazil. herbert@biof.ufrj.br.
authors.forename: Herbert Leonel
authors.initials: HL
authors.lastname: de Matos Guedes
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D056747:Immunomodulation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007894:Leishmania mexicana / Q000276:immunology* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D016207:Cytokines; D016052:Protozoan Vaccines; D007371:Interferon-gamma
keywords: ADDAVAX®; C57BL/6; Intranasal vaccine; LaAg; Leishmania amazonensis; Leishmaniasis