Lage Daniela P, Machado Amanda S, Vale Danniele L, Freitas Camila S, Linhares Flávia P, Cardoso Jamille M O, Pereira Isabela A G, Ramos Fernanda F, Tavares Grasiele S V, Ludolf Fernanda, Oliveira-da-Silva João A, Bandeira Raquel S, Silva Alessandra M, Simões Luciana C, Reis Thiago A R, Oliveira Jamil S, Christodoulides Myron, Chávez-Fumagalli Miguel A, Roatt Bruno M, Martins Vívian T, Coelho Eduardo A F
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil.
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Departamento de Ciências Biológicas, Insituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Cytokine. 2022 May;153:155865. doi: 10.1016/j.cyto.2022.155865. Epub 2022 Mar 23.
Leishmania virulence proteins should be considered as vaccine candidates against disease, since they are involved in developing infection in mammalian hosts. In a previous study, a Leishmania guanosine-5'-triphosphate (GTP)-binding protein was identified as a potential parasite virulence factor. In the present work, the gene encoding GTP was cloned and the recombinant protein (rGTP) was evaluated as a vaccine candidate against Leishmania infantum infection. The protein was associated with saponin (rGTP/Sap) or Poloxamer 407-based micelles (rGTP/Mic) as adjuvants, and protective efficacy was investigated in BALB/c mice after parasite challenge. Both rGTP/Sap and rGTP/Mic compositions induced a Th1-type immune response in vaccinated animals, with significantly higher levels of IFN-γ, IL-12, IL-2, TNF-α, GM-CSF, nitrite, specific IgG2a isotype antibody and positive lymphoproliferation, when compared to the control groups. This response was accompanied by significantly lower parasite load in the spleens, livers, bone marrows and draining lymph nodes of the animals. Immunological and parasitological evaluations indicated that rGTP/Mic induced a more polarized Th1-type response and higher reduction in the organ parasitism, and with lower hepatotoxicity, when compared to the use of rGTP/Sap. In conclusion, our preliminary data suggest that rGTP could be considered for further development as a vaccine candidate to protect against VL.
利什曼原虫毒力蛋白应被视为抗该疾病的疫苗候选物，因为它们参与在哺乳动物宿主中引发感染。在先前的一项研究中，一种利什曼原虫鸟苷 - 5'-三磷酸（GTP）结合蛋白被鉴定为潜在的寄生虫毒力因子。在本研究中，克隆了编码GTP的基因，并评估了重组蛋白（rGTP）作为抗婴儿利什曼原虫感染的疫苗候选物。该蛋白与皂苷（rGTP/Sap）或泊洛沙姆407基胶束（rGTP/Mic）作为佐剂结合，并在寄生虫攻击后在BALB/c小鼠中研究其保护效果。与对照组相比，rGTP/Sap和rGTP/Mic组合物在接种动物中均诱导了Th1型免疫反应，IFN-γ、IL-12、IL-2、TNF-α、GM-CSF、亚硝酸盐、特异性IgG2a同种型抗体水平和阳性淋巴细胞增殖显著更高。这种反应伴随着动物脾脏、肝脏、骨髓和引流淋巴结中寄生虫负荷的显著降低。免疫学和寄生虫学评估表明，与使用rGTP/Sap相比，rGTP/Mic诱导了更极化的Th1型反应，器官寄生虫感染减少更多，且肝毒性更低。总之，我们的初步数据表明，rGTP可考虑进一步开发为预防内脏利什曼病的疫苗候选物。
