A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis.
A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis.
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DOI：
10.1186/s12879-016-1444-z
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发表时间：
2016-03-05
影响因子：
3.7
通讯作者：
Ndao M
中科院分区：
文献类型：
--
作者：
Ricciardi A;Visitsunthorn K;Dalton JP;Ndao M
由于其对公众健康的影响，血吸虫病是最重要的人类蠕虫感染。临床表现是慢性的，并显着降低个人的生活质量。感染者患有长期的器官病变，包括最终导致器官衰竭的纤维化。针对这种寄生虫病的疫苗的开发将有助于长期减少疾病谱和传播。我们的小组选择曼氏血吸虫 (Sm) 组织蛋白酶 B（一种参与寄生虫摄食的肽酶）作为潜在的候选疫苗。我们的实验制剂由在 Montanide ISA 720 VG 中配制的重组 Sm-组织蛋白酶 B 组成，Montanide ISA 720 VG 是一种基于角鲨烯的佐剂，含有甘露醇单油酸酯乳化剂。通过测定每只小鼠的成虫、肝虫卵和肠虫卵数量来评估寄生虫负荷。 ELISA 中使用血清来评估抗原特异性抗体的产生，并用抗原刺激分离的脾细胞以分析细胞因子分泌水平。 Sm-组织蛋白酶 B 和 Montanide 制剂通过显着减少所有形式的寄生虫负担来提供针对攻击感染的保护。与对照组相比，免疫动物的蠕虫负荷、肝卵负荷和肠道卵负荷分别降低了 60%、62% 和 56%（分别为 P = 0.0002、P < 0.0001、P = 0.0009）。疫苗免疫引发了 Sm-组织蛋白酶 B 特异性抗体的大量产生（终点滴度 = 122,880）。观察到抗原特异性 IgG1 和 IgG2c 滴度，其中前者的滴度更高。此外，与对照动物相比，从免疫动物中分离的脾细胞在用重组 Sm-组织蛋白酶 B 刺激时，分泌更高水平的关键 Th1 细胞因子、IFN-γ、IL-12 和 TNF-α，以及 Th2 细胞因子 IL-5 和 IL-4。与对照动物相比，免疫动物中的 Th17 细胞因子 IL-17、趋化因子 CCL5 和生长因子 GM-CSF 也显着增加。到控件。本研究中测试的制剂能够显着减少所有形式的寄生虫负担，刺激抗原特异性抗体的强劲产生，并诱导混合 Th1/Th2 反应。这些结果凸显了 Sm-组织蛋白酶 B/Montanide ISA 720 VG 作为血吸虫病候选疫苗的潜力。本文的在线版本 (doi:10.1186/s12879-016-1444-z) 包含补充材料，可供授权用户使用。
Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. Our group has chosen Schistosoma mansoni (Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels. The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (P = 0.0002, P < 0.0001, P = 0.0009, respectively). Immunizations with the vaccine elicited robust production of Sm-cathepsin B specific antibodies (endpoint titers = 122,880). Both antigen-specific IgG1 and IgG2c titers were observed, with the former having more elevated titers. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, secreted higher levels of key Th1 cytokines, IFN-γ, IL-12, and TNF-α, as well as the Th2 cytokines IL-5 and IL-4 when stimulated with recombinant Sm-cathepsin B. The Th17 cytokine IL-17, the chemokine CCL5, and the growth factor GM-CSF were also significantly increased in the immunized animals compared to the controls. The formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis. The online version of this article (doi:10.1186/s12879-016-1444-z) contains supplementary material, which is available to authorized users.