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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.
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