Wang Wei, Liu Fei, Jiang Ning, Lu Huijun, Yang Na, Feng Ying, Sang Xiaoyu, Cao Yaming, Chen Qijun
Key Laboratory of Zoonosis, Jilin University, Changchun, China.
Department of Immunology, China Medical University, Shenyang, China.
Front Microbiol. 2018 May 18;9:1023. doi: 10.3389/fmicb.2018.01023. eCollection 2018.
The TatD-like DNase of species has previously been characterized as a conserved antigen that plays an important role in immune evasion. Here, we found that TatD-like DNase is expressed, apart from the erythrocytic stage, throughout the developmental stages of the parasite in the mosquito vector. Antibodies to the molecule significantly blocked parasites development and transition in the mosquito gut. Further, mice immunized with recombinant TatD-like DNase showed significant resistance to parasite challenge. The antigenicity of the TatD-like antigen in combination with various adjuvants, including Freund's adjuvants, Montanide ISA 51 and 61, Alhydrogel (aluminum hydroxide), and levamisole was investigated. It was found that immunization of the recombinant TatD-like DNase in combination with Montanide ISA 51 induced strong responses that showed significant protection against parasite challenge in a mouse model. The data further support that TatD-like DNase is a functionally important molecule in the whole development cycle of the malaria parasites and a candidate for malaria vaccine development.
该物种的类TatD脱氧核糖核酸酶先前已被鉴定为一种保守抗原,在免疫逃避中起重要作用。在此,我们发现,除红细胞阶段外,类TatD脱氧核糖核酸酶在疟原虫于蚊媒中的整个发育阶段均有表达。针对该分子的抗体显著阻断了疟原虫在蚊肠道内的发育和转化。此外,用重组类TatD脱氧核糖核酸酶免疫的小鼠对疟原虫攻击表现出显著抗性。研究了类TatD抗原与各种佐剂(包括弗氏佐剂、Montanide ISA 51和61、氢氧化铝凝胶和左旋咪唑)联合使用时的抗原性。结果发现,重组类TatD脱氧核糖核酸酶与Montanide ISA 51联合免疫诱导了强烈反应,在小鼠模型中显示出对疟原虫攻击的显著保护作用。这些数据进一步支持类TatD脱氧核糖核酸酶是疟原虫整个发育周期中功能上重要的分子,也是疟疾疫苗开发的候选分子。