Identification of immunodominant antigens from a first-generation vaccine against cutaneous Leishmaniasis

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dc.contributorLab. Bioquímicapt_BR
dc.contributor.authorGermanó, María Josépt_BR
dc.contributor.authorMackern-Oberti1, Juan Pablopt_BR
dc.contributor.authorVitório, Jessica Gardonept_BR
dc.contributor.authorDuarte, Mariana Costapt_BR
dc.contributor.authorPimenta, Daniel Carvalhopt_BR
dc.contributor.authorSanchez, Maria Victoriapt_BR
dc.contributor.authorBruna, Flavia Alejandrapt_BR
dc.contributor.authorLozano, Esteban Sebastiánpt_BR
dc.contributor.authorFernandes, Ana Paulapt_BR
dc.contributor.authorCargnelutti, Diego Estebanpt_BR
dc.date.accessioned2022-06-02T19:41:43Z-
dc.date.available2022-06-02T19:41:43Z-
dc.date.issued2022pt_BR
dc.identifier.citationGermanó MJ, Mackern-Oberti1 JP, Vitório JG, Duarte MC, Pimenta DC, Sanchez MV, et al. Identification of immunodominant antigens from a first-generation vaccine against cutaneous Leishmaniasis. Front. Immunol. 2022 May;13:825007. doi:10.3389/fimmu.2022.825007.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/4379-
dc.description.abstractLeishmaniasis is a neglected tropical disease (NTD) caused by parasites belonging to the Leishmania genus for which there is no vaccine available for human use. Thus, the aims of this study are to evaluate the immunoprotective effect of a first-generation vaccine against L. amazonensis and to identify its immunodominant antigens. BALB/c mice were inoculated with phosphate buffer sodium (PBS), total L. amazonensis antigens (TLAs), or TLA with Poly (I:C) and Montanide ISA 763. The humoral and cellular immune response was evaluated before infection. IgG, IgG1, and IgG2a were measured on serum, and IFN-γ, IL-4, and IL-10 cytokines as well as cell proliferation were measured on a splenocyte culture from vaccinated mice. Immunized mice were challenged with 104 infective parasites of L. amazonensis on the footpad. After infection, the protection provided by the vaccine was analyzed by measuring lesion size, splenic index, and parasite load on the footpad and spleen. To identify immunodominant antigens, total proteins of L. amazonensis were separated on 2D electrophoresis gel and transferred to a membrane that was incubated with serum from immunoprotected mice. The antigens recognized by the serum were analyzed through a mass spectrometric assay (LC-MS/MS-IT-TOF) to identify their protein sequence, which was subjected to bioinformatic analysis. The first-generation vaccine induced higher levels of antibodies, cytokines, and cell proliferation than the controls after the second dose. Mice vaccinated with TLA + Poly (I:C) + Montanide ISA 763 showed less footpad swelling, a lower splenic index, and a lower parasite load than the control groups (PBS and TLA). Four immunodominant proteins were identified by mass spectrometry: cytosolic tryparedoxin peroxidase, an uncharacterized protein, a kinetoplast-associated protein-like protein, and a putative heat-shock protein DNAJ. The identified proteins showed high levels of conserved sequence among species belonging to the Leishmania genus and the Trypanosomatidae family. These proteins also proved to be phylogenetically divergent to human and canine proteins. TLA + Poly (I:C) + Montanide ISA 763 could be used as a first-generation vaccine against leishmaniasis. The four proteins identified from the whole-protein vaccine could be good antigen candidates to develop a new-generation vaccine against leishmaniasis.pt_BR
dc.description.sponsorship(UNCUYO) Universidad Nacional de Cuyopt_BR
dc.description.sponsorship(CONICET) National Scientific and Technical Research Councilpt_BR
dc.description.sponsorship(ANPCyT) Agencia Nacional de Promoción Científica y Tecnológicapt_BR
dc.description.sponsorship(UDA) Universidad del Aconcaguapt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(FAPEMIG) Fundação de Amparo à Pesquisa do Estado de Minas Geraispt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.format.extent825007pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofFrontiers in Immunologypt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleIdentification of immunodominant antigens from a first-generation vaccine against cutaneous Leishmaniasispt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.3389/fimmu.2022.825007pt_BR
dc.identifier.urlhttps://doi.org/10.3389/fimmu.2022.825007pt_BR
dc.contributor.external(IMBECU) instituto de Medicina y Biología Experimental de Cuyopt_BR
dc.contributor.external(CONICET) Consejo Nacional de Investigaciones Cientificas y Tecnicaspt_BR
dc.contributor.external(UNCuyo) Universidad Nacional de Cuyopt_BR
dc.contributor.external(UFMG) Universidade Federal de Minas Geraispt_BR
dc.identifier.citationvolume13pt_BR
dc.subject.keywordL. amazonensispt_BR
dc.subject.keywordimmunoproteomic analysispt_BR
dc.subject.keywordvaccinespt_BR
dc.subject.keywordAmerican tegumentary leishmaniasispt_BR
dc.subject.keywordneglected tropical disease (NTD)pt_BR
dc.relation.ispartofabbreviatedFront. Immunolpt_BR
dc.identifier.citationabntv. 13, 825007, maio. 2022pt_BR
dc.identifier.citationvancouver2022 May;13:825007pt_BR
dc.contributor.butantanPimenta, Daniel Carvalho|:Pesquisador:Docente permanente PPGTOX|:Lab. Bioquímicapt_BR
dc.sponsorship.butantan(UNCUYO) Universidad Nacional de Cuyo¦¦UNCuyo SIIP 06/J499pt_BR
dc.sponsorship.butantan(UNCUYO) Universidad Nacional de Cuyo¦¦UNCuyo SIIP J082/2019pt_BR
dc.sponsorship.butantan(CONICET) National Scientific and Technical Research Council¦¦PIP 11220150100210Co 2015-2017pt_BR
dc.sponsorship.butantan(CONICET) National Scientific and Technical Research Council¦¦PIP 0081-2015pt_BR
dc.sponsorship.butantan(ANPCyT) Agencia Nacional de Promoción Científica y Tecnológica¦¦PICT 2018-01511pt_BR
dc.sponsorship.butantan(ANPCyT) Agencia Nacional de Promoción Científica y Tecnológica¦¦PICT-2015-0271pt_BR
dc.sponsorship.butantan(ANPCyT) Agencia Nacional de Promoción Científica y Tecnológica¦¦PICT 2015-1052pt_BR
dc.sponsorship.butantan(ANPCyT) Agencia Nacional de Promoción Científica y Tecnológica¦¦PICT 2018-2642pt_BR
dc.sponsorship.butantan(ANPCyT) Agencia Nacional de Promoción Científica y Tecnológica¦¦PICT 2019-01762pt_BR
dc.sponsorship.butantan(UDA) Universidad del Aconcagua¦¦pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦465293/2014-0pt_BR
dc.sponsorship.butantan(FAPEMIG) Fundação de Amparo à Pesquisa do Estado de Minas Gerais¦¦red001214pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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