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A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection

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dc.creatorDaniela Pagliara Lage
dc.creatorJoão Augusto Oliveira-da-silva
dc.creatorFernanda Fonseca Ramos
dc.creatorGrasiele de Sousa Vieira Tavares
dc.creatorFernanda Ludolf Ribeiro
dc.creatorRaquel S. Bandeira
dc.creatorIsabela A. G. Pereira
dc.creatorMiguel Angel Chaves Fumagalli
dc.creatorBruno Mendes Roatt
dc.creatorRicardo A. Machado-de-ávila
dc.creatorMyron Christodoulides
dc.creatorDanniele Luciana Vale
dc.creatorEduardo Antonio Ferraz Coelho
dc.creatorVívian Tamietti Martins
dc.creatorFlávia P. Linhares
dc.creatorCamila Simões de Freitas
dc.creatorAmanda Sanchez Machado
dc.creatorJamile M. O. Cardoso
dc.creatorDaysiane de Oliveira
dc.creatorNathalia Coral Galvani
dc.creatorMarcelo P. de Oliveira
dc.date.accessioned2023-11-06T20:47:34Z
dc.date.accessioned2025-09-09T00:10:44Z
dc.date.available2023-11-06T20:47:34Z
dc.date.issued2022
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.3390/vaccines10071146
dc.identifier.issn2076-393X
dc.identifier.urihttps://hdl.handle.net/1843/60528
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofVaccines
dc.rightsAcesso Aberto
dc.subjectVacinação
dc.subjectCélulas T.
dc.subjectPeptídeos
dc.subjectImunidade
dc.subject.otherVisceral leishmaniasis
dc.subject.otherVaccine
dc.subject.otherT-cell epitopes
dc.subject.otherPolypeptide-based protein
dc.subject.otherImmune response
dc.subject.otherAdjuvants
dc.titleA Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection
dc.typeArtigo de periódico
local.citation.epage22
local.citation.issue7
local.citation.spage1146
local.citation.volume10
local.description.resumoCurrently, there is no licensed vaccine to protect against human visceral leishmaniasis (VL), a potentially fatal disease caused by infection with Leishmania parasites. In the current study, a recombinant chimeric protein ChimT was developed based on T-cell epitopes identified from the immunogenic Leishmania amastigote proteins LiHyp1, LiHyV, LiHyC and LiHyG. ChimT was associated with the adjuvants saponin (Sap) or monophosphoryl lipid A (MPLA) and used to immunize mice, and their immunogenicity and protective efficacy were evaluated. Both ChimT/Sap and ChimT/MPLA induced the development of a specific Th1-type immune response, with significantly high levels of IFN-γ, IL-2, IL-12, TNF-α and GM-CSF cytokines produced by CD4+ and CD8+ T cell subtypes (p < 0.05), with correspondingly low production of anti-leishmanial IL-4 and IL-10 cytokines. Significantly increased (p < 0.05) levels of nitrite, a proxy for nitric oxide, and IFN-γ expression (p < 0.05) were detected in stimulated spleen cell cultures from immunized and infected mice, as was significant production of parasite-specific IgG2a isotype antibodies. Significant reductions in the parasite load in the internal organs of the immunized and infected mice (p < 0.05) were quantified with a limiting dilution technique and quantitative PCR and correlated with the immunological findings. ChimT/MPLA showed marginally superior immunogenicity than ChimT/Sap, and although this was not statistically significant (p > 0.05), ChimT/MPLA was preferred since ChimT/Sap induced transient edema in the inoculation site. ChimT also induced high IFN-γ and low IL-10 levels from human PBMCs isolated from healthy individuals and from VL-treated patients. In conclusion, the experimental T-cell multi-epitope amastigote stage Leishmania vaccine administered with adjuvants appears to be a promising vaccine candidate to protect against VL.
local.identifier.orcidhttps://orcid.org/0000-0001-7882-215X
local.identifier.orcidhttps://orcid.org/0000-0002-7852-0300
local.identifier.orcidhttps://orcid.org/0000-0002-8394-4802
local.identifier.orcidhttps://orcid.org/0000-0002-1303-0490
local.identifier.orcidhttps://orcid.org/0000-0002-9663-4731
local.identifier.orcidhttps://orcid.org/0000-0002-6681-9014
local.publisher.countryBrasil
local.publisher.departmentMED - DEPARTAMENTO DE CLÍNICA MÉDICA
local.publisher.departmentMEDICINA - FACULDADE DE MEDICINA
local.publisher.initialsUFMG
local.url.externahttps://www.mdpi.com/2076-393X/10/7/1146

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