title: A recombinant fusion protein displaying murine and human MHC class I- and II-specific epitopes protects against Leishmania amazonensis infection.
abstract: Tegumentary leishmaniasis (TL) constitutes a major public health problem with significant morbidity worldwide. Synthetic peptide-based vaccines are attractive candidates to protect against leishmaniasis, since T cell-specific epitopes can be delivery to antigen-presenting cells, leading to the generation of a Th1 cell-mediated immunity. In this context, the present study aims to evaluate the immunogenicity and protective efficacy of a vaccine composed of major histocompatibility complex class I and II-restricted epitopes derived from four Leishmania infantum proteins to protect mice against Leishmania amazonensis infection. This recombinant fusion protein was administered in BALB/c mice alone or with saponin. As controls, animals received saline or saponin. In the results, the administration of the recombinant protein plus saponin induced a specific IFN-γ, IL-12 and GM-CSF production, as well as high IgG2a isotype antibody levels, which protected mice against a challenge using L. amazonensis promastigotes. Lower parasite burden was found in the infected footpads, liver, spleen and draining lymph node of vaccinated mice, when compared to those from the control groups. In addition, protection was associated with a lower IL-4 and IL-10 response, which was accompanied by the antileishmanial nitrite production by spleen cells of the animals. Interestingly, the recombinant protein administered alone induced a partial protection against challenge. In conclusion, this study shows a new vaccine candidate based on T cell-specific epitopes that was able to induce protection against L. amazonensis infection.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil; Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Vívian T
authors.initials: VT
authors.lastname: Martins
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Lage
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, Coltec, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Duarte
authors.affiliation: Departamento de Patologia Clínica, Coltec, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Maria R S
authors.initials: AM
authors.lastname: Carvalho
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lourena E
authors.initials: LE
authors.lastname: Costa
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tiago A O
authors.initials: TA
authors.lastname: Mendes
authors.affiliation: Departamento de Patologia Clínica, Coltec, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Danniele L
authors.initials: DL
authors.lastname: Vale
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, Coltec, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Menezes-Souza
authors.affiliation: Departamento de Patologia Clínica, Coltec, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Roatt
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carlos A P
authors.initials: CA
authors.lastname: Tavares
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 30130-100 Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, Coltec, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: eduardoferrazcoelho@yahoo.com.br.
authors.forename: Eduardo A F
authors.initials: EA
authors.lastname: Coelho
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D018314:Leishmania infantum / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology* / Q000517:prevention & control; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D054332:Leishmaniasis Vaccines; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit
keywords: CD4(+) T cells; CD8(+) T cells; Leishmania amazonensis; Polypeptide vaccine; Tegumentary leishmaniasis; Th1 immune response