Abstract
BackgroundWe 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.MethodsC57BL/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.ResultsC57BL/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.ConclusionThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1822-9) contains supplementary material, which is available to authorized users.
Highlights
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
Characterization of the partially resistant model of L. amazonensis infection in C57BL/6 mice To characterize the chronic mouse model of infection using L. amazonensis Josefa strain in C57BL/6 mice, we evaluated mice from different animal facilities: UNICAMP (Fig. 1a), FIOCRUZ (Fig. 1c), UFRJ (Fig. 1e) and UFF (Fig. 1g)
All mice presented a similar profile after L. amazonensis infection, with lesion progression until days 42–60 post-infection followed by a partial resolution of the lesion, with chronic parasite persistence (Fig. 1, Table 1)
Summary
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. In Brazil, infections with L. amazonensis used to be concentrated in the North of the country (Amazon Forest Region) [3]. In Manaus, 8 % of cutaneous infections were caused by L. amazonensis [4]. Since 2005, the Brazilian Ministry of Health has demonstrated the presence of L. amazonensis in all regions of Brazil [3]. The concern about L. amazonensis in Brazil relates to all forms of disease, including visceral and mucosal leishmaniasis [5] and the refractoriness to treatment of serious forms of the infection [6]. Difficulty in access to the regions affected by the disease hinders treatment efforts [3], the best strategy is prevention through vaccination
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