Leishmania eukaryotic elongation Factor-1 beta protein is immunogenic and induces parasitological protection in mice against Leishmania infantum infection

被引:5
|
作者
Santos, Thais T. O. [1 ]
Machado, Amanda S. [1 ]
Ramos, Fernanda F. [1 ]
Oliveira-da-Silva, Joao A. [1 ]
Lage, Daniela P. [1 ]
Tavares, Grasiele S., V [1 ]
Mendonca, Debora V. C. [1 ]
Cardoso, Mariana S. [2 ]
Siqueira, Williane F. [2 ]
Martins, Vivian T. [1 ]
Ludolf, Fernanda [1 ]
Reis, Thiago A. R. [1 ]
Carvalho, Livia M. [3 ]
Freitas, Camila S. [1 ]
Bandeira, Raquel S. [1 ]
Silva, Alessandra M. [1 ]
Oliveira, Jamil S. [4 ]
Moreira, Ricardo L. F. [5 ]
Fujiwara, Ricardo T. [2 ]
Roatt, Bruno M. [3 ]
Chavez-Fumagalli, Miguel A. [6 ]
Humbert, Maria, V [7 ]
Teixeira, Antonio L. [1 ,8 ]
Coelho, Eduardo A. F. [1 ]
机构
[1] Univ Fed Minas Gerais, Fac Med, Programa Posgrad Ciencias Saude Infectol & Med Tr, Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Belo Horizonte, MG, Brazil
[3] Univ Fed Ouro Preto, Lab Imunopatol, Nucleo Pesquisas Ciencias Biol NUPEB, Dept Ciencias Biol,Inst Ciencias Exatas & Biol, Ouro Preto, MG, Brazil
[4] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
[5] Hosp Eduardo Menezes, Fundacao Hosp Estado Minas Gerais, Belo Horizonte, MG, Brazil
[6] Univ Catolica Santa Maria, Urb San Jose S-N, Arequipa, Peru
[7] Univ Southampton, Southampton Gen Hosp, Sch Clin & Expt Sci, Neisseria Res Grp,Mol Microbiol,Fac Med, Southampton SO16 6YD, Hants, England
[8] Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, McGovern Med Sch, Neuropsychiat Program, Houston, TX USA
基金
英国医学研究理事会;
关键词
Visceral leishmaniasis; Eukaryotic elongation Factor-1 beta; Vaccine; Recombinant protein; DNA vaccine; Leishmania infantum;
D O I
10.1016/j.micpath.2021.104745
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Treatment for visceral leishmaniasis (VL) is hampered mainly by the toxicity and/or high cost of antileishmanial drugs. What is more, variability on sensitivity and/or specificity of diagnostic tests hinders effective disease management. In this context, prophylactic vaccination should be considered as a strategy to prevent disease. In the present study, immunogenicity of the Leishmania eukaryotic Elongation Factor-1 beta (EF1b) protein, classified as a Leishmania virulence factor, was evaluated in vitro and in vivo and tested, for the first time, as a vaccine candidate against Leishmania infantum infection. The antigen was administered as DNA vaccine or as recombinant protein (rEF1b) delivered in saponin. BALB/c mice immunization with a DNA plasmid and recombinant protein plus saponin induced development of specific Th1-type immunity, characterized by high levels of IFN-gamma, IL-12, GM-CSF, both T cell subtypes and antileishmanial IgG2a isotype antibodies, before and after infection. This immunological response to the vaccines was corroborated further by parasitological analysis of the vaccinated and then challenged mice, which showed significant reductions in the parasite load in their liver, spleen, bone marrow and draining lymph nodes, when compared to the controls. Vaccination using rEF1b/saponin induced a more robust Th1 response and parasitological protection when compared to the DNA vaccine. Furthermore, in vitro analysis of lymphoproliferation, IFN-gamma and IL-10 levels in human PBMC cultures showed as well development of a specific Th1-type response. In conclusion, data suggest that EF1b could be a promising vaccine candidate to protect against L. infantum infection.
引用
收藏
页数:9
相关论文
共 50 条
  • [41] Evaluation of a novel lentiviral vaccine expressing KMP11-HASPB fusion protein against Leishmania infantum in BALB/c mice
    Mortazavidehkordi, N.
    Farjadfar, A.
    Khanahmad, H.
    Najafabadi, Z. Ghayour
    Hashemi, N.
    Fallah, A.
    Najafi, A.
    Kia, V.
    Hejazi, S. H.
    PARASITE IMMUNOLOGY, 2016, 38 (11) : 670 - 677
  • [42] Recombinant guanosine-5'-triphosphate (GTP)-binding protein associated with Poloxamer 407-based polymeric micelles protects against Leishmania infantum infection
    Lage, Daniela P.
    Machado, Amanda S.
    Vale, Danniele L.
    Freitas, Camila S.
    Ramos, Fernanda F.
    Ludolf, Fernanda
    Oliveira-da-Silva, Joao A.
    Bandeira, Raquel S.
    Silva, Alessandra M.
    Simoes, Luciana C.
    Oliveira, Jamil S.
    Christodoulides, Myron
    Chavez-Fumagali, Miguel A.
    Roatt, Bruno M.
    Martins, Vivian T.
    Linhares, Flavia P.
    Cardoso, Jamille M. O.
    Pereira, Isabela A. G.
    Tavares, Grasiele S. V.
    Reis, Thiago A. R.
    Coelho, Eduardo A. F.
    CYTOKINE, 2022, 153
  • [43] Vaccination Route That Induces Transforming Growth Factor β Production Fails To Elicit Protective Immunity against Leishmania donovani Infection
    Bhowmick, Sudipta
    Mazumdar, Tuhina
    Ali, Nahid
    INFECTION AND IMMUNITY, 2009, 77 (04) : 1514 - 1523
  • [44] Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice
    Amit, Ajay
    Vijayamahantesh
    Dikhit, Manas R.
    Singh, Ashish Kumar
    Kumar, Vikash
    Suman, Shashi S.
    Singh, Ashu
    Kumar, Akhilesh
    Thakur, Ajit Kumar
    Das, Vidyanand Ravi
    Das, Pradeep
    Bimal, Sanjiva
    MOLECULAR IMMUNOLOGY, 2017, 82 : 104 - 113
  • [45] Alpha-galactosylceramide as adjuvant induces protective cell-mediated immunity against Leishmania mexicana infection in vaccinated BALB/c mice
    Diupotex, Mariana
    Zamora-Chimal, Jaime
    Cervantes-Sarabia, Rocely Buenaventura
    Salaiza-Suazo, Norma
    Becker, Ingeborg
    CELLULAR IMMUNOLOGY, 2023, 386
  • [46] Immunization of Experimental Dogs With Salivary Proteins From Lutzomyia longipalpis, Using DNA and Recombinant Canarypox Virus Induces Immune Responses Consistent With Protection Against Leishmania infantum
    Costa Abbehusen, Melissa Moura
    Cunha, Jurema
    Suarez, Martha Sena
    Teixeira, Clarissa
    Almeida, Valter dos Anjos
    Pereira, Lais da Silva
    Bordoni, Marcelo
    Gil-Santana, Leonardo
    Solca, Manuela da Silva
    Mote Fraga, Deborah Bittencourt
    Fischer, Laurent
    Bozza, Patricia Torres
    Valenzuela, Jesus G.
    Kamhawi, Shaden
    Andrade, Bruno B.
    Brodskyn, Claudia I.
    FRONTIERS IN IMMUNOLOGY, 2018, 9
  • [47] Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against Leishmania infantum infection
    Ramos, Fernanda Fonseca
    Costa, Lourena Emanuele
    Dias, Daniel Silva
    Oliveira Santos, Thais Teodoro
    Rodrigues, Marcella Rezende
    Lage, Daniela Pagliara
    Silveira Salles, Beatriz Cristina
    Martins, Vivian Tamietti
    Fernandes Ribeiro, Patricia Aparecida
    Chavez-Fumagalli, Miguel Angel
    Silva Dias, Ana Carolina
    Alves, Patricia Terra
    Marciano Vieira, Erica Leandro
    Roatt, Bruno Mendes
    Menezes-Souza, Daniel
    Duarte, Mariana Costa
    Teixeira, Antonio Lucio
    Goulart, Luiz Ricardo
    Ferraz Coelho, Eduardo Antonio
    PARASITES & VECTORS, 2017, 10
  • [48] Heterologous priming-boosting with DNA and vaccinia virus expressing kinetoplastid membrane protein-11 induces potent cellular immune response and confers protection against infection with antimony resistant and sensitive strains of Leishmania (Leishmania) donovani
    Guha, Rajan
    Das, Shantanabha
    Ghosh, June
    Naskar, Kshudiram
    Mandala, Ashok
    Sundar, Shyam
    Dujardin, Jean Claude
    Roy, Syamal
    VACCINE, 2013, 31 (15) : 1905 - 1915
  • [49] Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against Leishmania infantum infection
    Fernanda Fonseca Ramos
    Lourena Emanuele Costa
    Daniel Silva Dias
    Thaís Teodoro Oliveira Santos
    Marcella Rezende Rodrigues
    Daniela Pagliara Lage
    Beatriz Cristina Silveira Salles
    Vívian Tamietti Martins
    Patrícia Aparecida Fernandes Ribeiro
    Miguel Angel Chávez-Fumagalli
    Ana Carolina Silva Dias
    Patrícia Terra Alves
    Érica Leandro Marciano Vieira
    Bruno Mendes Roatt
    Daniel Menezes-Souza
    Mariana Costa Duarte
    Antonio Lúcio Teixeira
    Luiz Ricardo Goulart
    Eduardo Antonio Ferraz Coelho
    Parasites & Vectors, 10
  • [50] Short-term protection conferred by Leishvacin® against experimental Leishmania amazonensis infection in C57BL/6 mice
    Heitor Carneiro, Matheus Batista
    de Andrade e Sousa, Louisa Maria
    Vaz, Leonardo Gomes
    Dos Santos, Liliane Martins
    Vilela, Luciano
    de Souza, Carolina Carvalho
    Goncalves, Ricardo
    Tafuri, Wagner Luis
    Crocco Afonso, Luis Carlos
    Cortes, Denise Fonseca
    Vieira, Leda Quercia
    PARASITOLOGY INTERNATIONAL, 2014, 63 (06) : 826 - 834