Machado Amanda S, Lage Daniela P, 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, Simões Aratti C, Duarte Mariana C, 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.
Acta Trop. 2022 Jun;230:106412. doi: 10.1016/j.actatropica.2022.106412. Epub 2022 Mar 16.
Vaccination against visceral leishmaniasis (VL) should be considered as a control measure to protect against disease, and amastigote-specific proteins could help to develop such vaccines, since this parasite form is in contact with the host immune system during the active disease. In this study, a Leishmania amastigote-specific protein, LiHyG, was evaluated as recombinant protein (rLiHyG) as vaccine candidate against Leishmania infantum infection in BALB/c mice. The protein was associated with saponin (rLiHyG/Sap) or Poloxamer 407-based polymeric micelles (rLiHyG/Mic) as adjuvants, and animals receiving saline, saponin or micelle as controls. Immunological and parasitological analyses were performed before (n = 8 per group; as primary endpoint) and after (n = 8 per group; as secondary endpoint) infection. Results showed that, in both endpoints, rLiHyG/Sap and rLiHyG/Mic induced higher levels of IFN-γ, IL-12 and GM-CSF in spleen cell cultures from vaccinated animals, besides elevated presence of IgG2a isotype antibodies. Decreased hepatotoxicity and 'positive lymphoproliferative response were also found after challenge. Such findings reflected in significantly lower levels of parasite load found in their spleens, livers, bone marrows and draining lymph nodes. In conclusion, rLiHyG associated with Th1-type adjuvant could be considered for future studies as vaccine candidate to protect against VL.
内脏利什曼病（VL）疫苗接种应被视为预防该疾病的一项控制措施，而无鞭毛体特异性蛋白有助于开发此类疫苗，因为在活动性疾病期间，这种寄生虫形式会与宿主免疫系统接触。在本研究中，评估了一种利什曼原虫无鞭毛体特异性蛋白LiHyG作为重组蛋白（rLiHyG），作为BALB/c小鼠抗婴儿利什曼原虫感染的候选疫苗。该蛋白与皂苷（rLiHyG/Sap）或基于泊洛沙姆407的聚合物胶束（rLiHyG/Mic）作为佐剂结合，接受生理盐水、皂苷或胶束的动物作为对照。在感染前（每组n = 8；作为主要终点）和感染后（每组n = 8；作为次要终点）进行免疫和寄生虫学分析。结果表明，在两个终点中，rLiHyG/Sap和rLiHyG/Mic除了使IgG2a同种型抗体水平升高外，还在接种动物的脾细胞培养物中诱导了更高水平的IFN-γ、IL-12和GM-CSF。攻击后还发现肝毒性降低和“阳性淋巴细胞增殖反应”。这些发现反映在其脾脏、肝脏、骨髓和引流淋巴结中发现的寄生虫载量显著降低。总之，与Th1型佐剂结合的rLiHyG可作为预防VL的候选疫苗用于未来研究。
