Man Suqin, Fu Yongfeng, Guan Yue, Feng Meng, Qiao Ke, Li Xueping, Gao Hongjian, Cheng Xunjia
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Electron Microscopy, School of Basic Medical Science, Fudan University, Shanghai, China.
Front Microbiol. 2017 Dec 19;8:2545. doi: 10.3389/fmicb.2017.02545. eCollection 2017.
species are tick-borne intraerythrocytic protozoa that cause babesiosis in humans worldwide. No vaccine has yet proven effective against infection. Surface antigens of merozoites are involved in the invasion of erythrocytes by . Surface antigens may be presented by both babesial sporozoites and merozoites and provide a general target for antibody-mediated inhibition of erythrocyte invasion. Here we evaluated a major surface antigen of merozoites, BMSA, as a potential vaccine to prevent babesiosis. Our data indicated that is transcribed during different phases, including ring form, amoeboid form, and merozoites, and that its expression is significantly increased in mature merozoites. The protein was found to be located in the membrane of and in the cytoplasm of infected erythrocytes. The immune response induced by BMSA had a significant inhibitory effect on parasite invasion of the host erythrocytes (83.3% inhibition of invasion) and parasite growth . The levels of parasitemia significantly decreased after BMSA vaccination when mice were infected with babesia parasite. Importantly, protective immunity was significantly related to the upregulation of the Th17 cytokine interleukin-17, the Th1 cytokine interleukin-12p70 and the Th2 cytokines, such as interleukin-4, -6, and -10. Ingenuity Pathway Analysis indicated that interleukin-17 facilitated the secretion of Th2 cytokines, such as interleukin-10, -4, and -6, thereby inducing a predominately Th2 protective immune response and promoting the expression a high level of special IgG1 against infection. Further, an anti-BMSA monoclonal antibody successfully protected NOD/SCID mice from a challenge with . Taken together, our results indicated that BMSA induces a protective immune response against infection and may serve as a potential vaccine.
巴贝斯虫是通过蜱传播的细胞内原生动物，可在全球范围内引发人类巴贝斯虫病。目前尚无疫苗被证明对该感染有效。裂殖子的表面抗原参与巴贝斯虫对红细胞的入侵。巴贝斯虫的子孢子和裂殖子均可呈现表面抗原，这为抗体介导的抑制红细胞入侵提供了一个通用靶点。在此，我们评估了巴贝斯虫裂殖子的一种主要表面抗原BMSA作为预防巴贝斯虫病的潜在疫苗。我们的数据表明，BMSA在包括环状体、阿米巴样体和裂殖子在内的不同阶段均有转录，且其表达在成熟裂殖子中显著增加。该蛋白定位于巴贝斯虫的膜上以及被感染红细胞的细胞质中。BMSA诱导的免疫反应对寄生虫入侵宿主红细胞具有显著抑制作用（入侵抑制率达83.3%），并抑制寄生虫生长。当小鼠感染巴贝斯虫寄生虫后，接种BMSA疫苗后虫血症水平显著降低。重要的是，保护性免疫与Th17细胞因子白细胞介素-17、Th1细胞因子白细胞介素-12p70以及Th2细胞因子如白细胞介素-4、-6和-10的上调显著相关。通路分析表明，白细胞介素-17促进了Th2细胞因子如白细胞介素-10、-4和-6的分泌，从而诱导了以Th2为主的保护性免疫反应，并促进了针对巴贝斯虫感染的高水平特异性IgG1的表达。此外，一种抗BMSA单克隆抗体成功保护NOD/SCID小鼠免受巴贝斯虫的攻击。综上所述，我们的结果表明，BMSA可诱导针对巴贝斯虫感染的保护性免疫反应，并可能成为一种潜在疫苗。
