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
  • [31] Protection against experimental visceral leishmaniasis infection in dogs immunized with purified excreted secreted antigens of Leishmania infantum promastigotes
    Lemesre, JL
    Holzmuller, P
    Cavaleyra, M
    Gonçalves, RB
    Hottin, G
    Papierok, G
    VACCINE, 2005, 23 (22) : 2825 - 2840
  • [32] Cysteine proteinase type III is protective against Leishmania infantum infection in BALB/c mice and highly antigenic in visceral leishmaniasis individuals
    Khoshgoo, Naghmeh
    Zahedifard, Farnaz
    Azizi, Hiva
    Taslimi, Yasaman
    Jimenez Alonso, Maribel
    Rafati, Sima
    VACCINE, 2008, 26 (46) : 5822 - 5829
  • [33] Adjuvanted vaccines driven protection against visceral infection in BALB/c mice by Leishmania donovani
    Goyal, Deepak Kumar
    Keshav, Poonam
    Kaur, Sukhbir
    MICROBIAL PATHOGENESIS, 2021, 151
  • [34] Cocktail of gp63 and Hsp70 induces protection against Leishmania donovani in BALB/c mice
    Kaur, T.
    Sobti, R. C.
    Kaur, S.
    PARASITE IMMUNOLOGY, 2011, 33 (02) : 95 - 103
  • [35] Leishmania tarentolae secreting the sand fly salivary antigen PpSP15 confers protection against Leishmania major infection in a susceptible BALB/c mice model
    Katebi, A.
    Gholami, E.
    Taheri, T.
    Zahedifard, F.
    Habibzadeh, S.
    Taslimi, Y.
    Shokri, F.
    Papadopoulou, B.
    Kamhawi, S.
    Valenzuela, J. G.
    Rafati, S.
    MOLECULAR IMMUNOLOGY, 2015, 67 (02) : 501 - 511
  • [36] Intranasal vaccination with killed Leishmania amazonensis promastigotes antigen (LaAg) associated with CAF01 adjuvant induces partial protection in BALB/c mice challenged with Leishmania (infantum) chagasi
    Leal, Janine Miranda
    Mosquini, Marcelle
    Covre, Luciana Polaco
    Stagmiller, Nataly Pescinalli
    Rodrigues, Rodrigo Ribeiro
    Christensen, Dennis
    De Matos Guedes, Herbert Leonel
    Rossi-Bergmann, Bartira
    De Oliviera Gomes, Daniel Claudio
    PARASITOLOGY, 2015, 142 (13) : 1640 - 1646
  • [37] Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice
    Martinez-Rodrigo, Abel
    Dias, Daniel S.
    Ribeiro, Patricia A. F.
    Roatt, Bruno M.
    Mas, Alicia
    Carrion, Javier
    Coelho, Eduardo A. F.
    Dominguez-Bernal, Gustavo
    VACCINES, 2019, 7 (04)
  • [38] Immunization with the Leishmania infantum recombinant cyclophilin protein 1 confers partial protection to subsequent parasite infection and generates specific memory T cells
    Santos-Gomes, G. M.
    Rodrigues, A.
    Teixeira, F.
    Carreira, J.
    Alexandre-Pires, G.
    Carvalho, S.
    Santos-Mateus, D.
    Martins, C.
    Vale-Gato, I.
    Marques, C.
    Tomas, A. M.
    VACCINE, 2014, 32 (11) : 1247 - 1253
  • [39] DNA vaccination with linear minimalistic (MIDGE) vectors confers protection against Leishmania major infection in mice
    López-Fuertes, L
    Pérez-Jiménez, E
    Vila-Coro, AJ
    Sack, F
    Moreno, S
    Konig, SA
    Junghans, C
    Wittig, B
    Timón, M
    Esteban, M
    VACCINE, 2002, 21 (3-4) : 247 - 257
  • [40] Antibiotic resistance free plasmid DNA expressing LACK protein leads towards a protective Th1 response against Leishmania infantum infection
    Ramos, I.
    Alonso, A.
    Peris, A.
    Marcen, J. M.
    Abengozar, M. A.
    Alcolea, P. J.
    Castillo, J. A.
    Larraga, V.
    VACCINE, 2009, 27 (48) : 6695 - 6703