The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy.

The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy.
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基于表位的日本血吸虫疫苗制剂中使用的亚基的性质和组合会影响其功效

DOI:
10.1186/1756-3305-3-109
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发表时间:
2010-11-19
影响因子:
3.2
通讯作者:
Su C
Su C
中科院分区:
医学2区
文献类型:
--
作者:
Wang X;Zhang L;Chi Y;Hoellwarth J;Zhou S;Wen X;He L;Liu F;Wu C;Su C

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背景血吸虫病仍然是流行国家的一个主要公共卫生问题,由三种主要血吸虫物种中的任何一种感染引起。尽管迄今为止还没有可用的疫苗,但这种策略似乎是可行的,因为在一生中反复感染的个体中会产生自然免疫力。由于导致 Th1 型和 Th2 型反应的疫苗接种已被证明有助于保护性免疫,因此能够刺激多臂免疫反应的疫苗制剂可能是最有效的。此前,我们开发了部分保护性、基于单 Th 细胞和 B 细胞表位的肽-DNA 双疫苗 (PDDV)(分别为 T3-PDDV 和 B3-PDDV),能够分别引发针对日本血吸虫 22.6 kDa 皮膜抗原 (Sj22.6) 和 62 kDa 肌球蛋白片段 (Sj62) 的免疫反应。 结果在本研究中,我们开发了含有多种成分的 PDDV 混合物S的表位。通过预测细胞毒性表位、辅助表位和 B 细胞表位,从 Sj22.6、Sj62 和 Sj97 抗原中提取日本日本杆菌,并评估体内疫苗潜力。结果显示,用单表位 PDDV 免疫的小鼠分别引发 Tc、Th 或 B 细胞反应,用 T3-或 B3-单表位 PDDV 制剂免疫的小鼠部分受到保护免受感染。然而,用多组分(3 个 PDDV 组分)制剂免疫的小鼠引发了可变的免疫反应,其免疫保护性低于单表位 PDDV 制剂。结论我们的数据表明,与单独施用每种组分相比,组合这些不同的抗原并没有产生更有效的疫苗制剂,并进一步表明,抗原不同的疫苗靶点免疫产生的免疫干扰可能是多组分疫苗制剂开发中的一个重要考虑因素。
BackgroundSchistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV) (T3-PDDV and B3-PDDV, respectively) capable of eliciting immune responses against theSchistosoma japonicum22.6 kDa tegument antigen (Sj22.6) and a 62 kDa fragment of myosin (Sj62), respectively.ResultsIn this study, we developed PDDV cocktails containing multiple epitopes ofS. japonicumfrom Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potentialin vivo. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components) formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations.ConclusionsOur data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.
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发表时间: 2008-07-01
影响因子: 3.1
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