Vivian T Martins1, Mariana C Duarte2,3, Miguel A Chávez-Fumagalli4, Daniel Menezes-Souza5,6, Cecília S P Coelho7, Danielle F de Magalhães-Soares8, Ana Paula Fernandes9, Manuel Soto10, Carlos A P Tavares11, Eduardo A F Coelho12,13,14. 1. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. viviantamietti@yahoo.com.br. 2. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. marianacostaduarte1@gmail.com. 3. Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. marianacostaduarte1@gmail.com. 4. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. miguel.fumagalli@pq.cnpq.br. 5. Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. daniel.ufop@gmail.com. 6. Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. daniel.ufop@gmail.com. 7. RW Bioprospection Ltda, Belo Horizonte, Minas Gerais, Brazil. cecilia_perilo@hotmail.com. 8. Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. danifm1@yahoo.com.br. 9. Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. apfernandes.ufmg@gmail.com. 10. Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain. msoto@cbm.uam.es. 11. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. capt@icb.ufmg.br. 12. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. eduardoferrazcoelho@yahoo.com.br. 13. Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. eduardoferrazcoelho@yahoo.com.br. 14. Laboratório de Biotecnologia Aplicada ao Estudo das Leishmanioses, Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31.270-901, Belo Horizonte, Minas Gerais, Brazil. eduardoferrazcoelho@yahoo.com.br.
Abstract
BACKGROUND: LiHyV is an antigenic hypothetical protein present in both promastigote and amastigote stages of Leishmania infantum, which was recently identified by an immunoproteomic approach. A recombinant version of this protein (rLiHyV) was evaluated as a diagnostic marker for canine VL (CVL). In addition, the prophylactic efficacy of the rLiHyV protein, and two of its CD8(+) T cell epitopes, has been analyzed in a murine model of visceral leishmaniasis (VL). METHODS: Initially, the rLiHyV protein was evaluated by an ELISA technique for the serodiagnosis of CVL. Secondly, vaccines composed of the recombinant protein and both chemically synthesized peptides, combined with saponin as an adjuvant; were administered subcutaneously into BALB/c mice. The cellular and humoral responses generated by vaccination were evaluated. In addition, the parasite burden and immune response were studied 10 weeks after L. infantum infection. RESULTS: The rLiHyV protein was recognized by antibodies of VL dogs. No cross-reactivity was obtained with sera from dogs vaccinated with a Brazilian commercial vaccine, with sera from animals infected with Trypanosoma cruzi, Babesia canis and Ehrlichia canis, or those from non-infected animals living in an endemic area for leishmaniasis. After challenge with L. infantum, spleen cells of BALB/c mice vaccinated with rLiHyV/saponin stimulated with parasite antigens showed a higher production of IFN-γ, IL-12 and GM-CSF, than the same cells obtained from mice vaccinated with the individual peptides, or mice from control (inoculated with saline or saponin) groups. This Th1-type cellular response observed in rLiHyV/saponin vaccinated mice was accompanied by the induction of parasite-specific IgG2a isotype antibodies. Animals immunized with rLiHyV/saponin showed significant reductions in the parasite burden in the liver, spleen, bone marrow and in the lymph nodes draining the paws relative to control mice. CONCLUSIONS: The present study showed for the first time that the L. infantum LiHyV protein could be considered as a vaccine candidate against L. infantum infection, as well as a diagnostic marker for CVL.
BACKGROUND: LiHyV is an antigenic hypothetical protein present in both promastigote and amastigote stages of Leishmania infantum, which was recently identified by an immunoproteomic approach. A recombinant version of this protein (rLiHyV) was evaluated as a diagnostic marker for canine VL (CVL). In addition, the prophylactic efficacy of the rLiHyV protein, and two of its CD8(+) T cell epitopes, has been analyzed in a murine model of visceral leishmaniasis (VL). METHODS: Initially, the rLiHyV protein was evaluated by an ELISA technique for the serodiagnosis of CVL. Secondly, vaccines composed of the recombinant protein and both chemically synthesized peptides, combined with saponin as an adjuvant; were administered subcutaneously into BALB/c mice. The cellular and humoral responses generated by vaccination were evaluated. In addition, the parasite burden and immune response were studied 10 weeks after L. infantum infection. RESULTS: The rLiHyV protein was recognized by antibodies of VL dogs. No cross-reactivity was obtained with sera from dogs vaccinated with a Brazilian commercial vaccine, with sera from animals infected with Trypanosoma cruzi, Babesia canis and Ehrlichia canis, or those from non-infected animals living in an endemic area for leishmaniasis. After challenge with L. infantum, spleen cells of BALB/c mice vaccinated with rLiHyV/saponin stimulated with parasite antigens showed a higher production of IFN-γ, IL-12 and GM-CSF, than the same cells obtained from mice vaccinated with the individual peptides, or mice from control (inoculated with saline or saponin) groups. This Th1-type cellular response observed in rLiHyV/saponin vaccinated mice was accompanied by the induction of parasite-specific IgG2a isotype antibodies. Animals immunized with rLiHyV/saponin showed significant reductions in the parasite burden in the liver, spleen, bone marrow and in the lymph nodes draining the paws relative to control mice. CONCLUSIONS: The present study showed for the first time that the L. infantum LiHyV protein could be considered as a vaccine candidate against L. infantum infection, as well as a diagnostic marker for CVL.
Authors: Miguel A Chávez-Fumagalli; Mariana A F Costa; Dulcilene M Oliveira; Laura Ramírez; Lourena E Costa; Mariana C Duarte; Vivian T Martins; Jamil S Oliveira; Carlos C Olortegi; Pedro Bonay; Carlos Alonso; Carlos A P Tavares; Manuel Soto; Eduardo A F Coelho Journal: Microbes Infect Date: 2010-07-01 Impact factor: 2.700
Authors: S Frankenburg; O Axelrod; S Kutner; C L Greenblatt; S N Klaus; E A Pirak; R McMaster; G H Lowell Journal: Vaccine Date: 1996-06 Impact factor: 3.641
Authors: Sassan Noazin; Farrokh Modabber; Ali Khamesipour; Peter G Smith; Lawrence H Moulton; Kiumarss Nasseri; Iraj Sharifi; Eltahir A G Khalil; Ivan Dario Velez Bernal; Carlos M F Antunes; Marie Paule Kieny; Marcel Tanner Journal: Vaccine Date: 2008-10-23 Impact factor: 3.641
Authors: Daniela P Lage; Vívian T Martins; Mariana C Duarte; Lourena E Costa; Esther Garde; Laura M Dimer; Amanda C S Kursancew; Miguel A Chávez-Fumagalli; Danielle F de Magalhães-Soares; Daniel Menezes-Souza; Bruno M Roatt; Ricardo A Machado-de-Ávila; Manuel Soto; Carlos A P Tavares; Eduardo A F Coelho Journal: Parasitol Res Date: 2016-01-19 Impact factor: 2.289
Authors: Robert G Schaut; Tara L Grinnage-Pulley; Kevin J Esch; Angela J Toepp; Malcolm S Duthie; Randall F Howard; Steven G Reed; Christine A Petersen Journal: Vaccine Date: 2016-09-21 Impact factor: 3.641
Authors: Letícia Martins Dos Reis Lage; José Mário Barichello; Daniela Pagliara Lage; Débora Vasconcelos Costa Mendonça; Ana Maria Ravena Severino Carvalho; Marcella Rezende Rodrigues; Daniel Menezes-Souza; Bruno Mendes Roatt; Ricardo José Alves; Carlos Alberto Pereira Tavares; Eduardo Antonio Ferraz Coelho; Mariana Costa Duarte Journal: Parasitol Res Date: 2016-07-01 Impact factor: 2.289
Authors: Monique Paiva Campos; Fabiano Borges Figueiredo; Fernanda Nazaré Morgado; Alinne Rangel Dos Santos Renzetti; Sara Maria Marques de Souza; Sandro Antônio Pereira; Rodrigo Nunes Rodrigues-Da-Silva; Josué Da Costa Lima-Junior; Paula Mello De Luca Journal: Front Immunol Date: 2018-07-25 Impact factor: 7.561
Authors: Juliana Ide Aoki; Sandra Marcia Muxel; Maria Fernanda Laranjeira-Silva; Ricardo Andrade Zampieri; Karl Erik Müller; Audun Helge Nerland; Lucile Maria Floeter-Winter Journal: Microb Genom Date: 2020-09-04
Authors: Mohammad Javad Abbaszadeh Afshar; Samira Elikaee; Reza Saberi; Sina Mohtasebi; Mehdi Mohebali Journal: BMC Vet Res Date: 2021-04-14 Impact factor: 2.741
Authors: Nathalia C Galvani; Amanda S Machado; Daniela P Lage; Camila S Freitas; Danniele L Vale; Daysiane de Oliveira; Fernanda Ludolf; Fernanda F Ramos; Bruna B Fernandes; Gabriel P Luiz; Débora V C Mendonça; João A Oliveira-da-Silva; Thiago A R Reis; Grasiele S V Tavares; Ana T Chaves; Nathalia S Guimarães; Unaí Tupinambás; Gláucia F Cota; Maria V Humbert; Vívian T Martins; Myron Christodoulides; Eduardo A F Coelho; Ricardo A Machado-de-Ávila Journal: Parasitol Res Date: 2021-10-19 Impact factor: 2.289
Authors: Rory C F De Brito; Jamille M De O Cardoso; Levi E S Reis; Joao F Vieira; Fernando A S Mathias; Bruno M Roatt; Rodrigo Dian D O Aguiar-Soares; Jeronimo C Ruiz; Daniela de M Resende; Alexandre B Reis Journal: Front Immunol Date: 2018-05-11 Impact factor: 7.561
Authors: Daniela P Lage; Patrícia A F Ribeiro; Daniel S Dias; Débora V C Mendonça; Fernanda F Ramos; Lívia M Carvalho; Bethina T Steiner; Grasiele S V Tavares; Vívian T Martins; Amanda S Machado; João A Oliveira-da-Silva; Thaís T O Santos; Camila S Freitas; Jamil S Oliveira; Bruno M Roatt; Ricardo A Machado-de-Ávila; Maria V Humbert; Myron Christodoulides; Eduardo A F Coelho Journal: Vaccines (Basel) Date: 2020-06-09