Wang Xuefeng, Zhang Lei, Chi Ying, Hoellwarth Jason, Zhou Sha, Wen Xiaoyun, He Lei, Liu Feng, Wu Calvin, Su Chuan
Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China.
Parasit Vectors. 2010 Nov 19;3:109. doi: 10.1186/1756-3305-3-109.
Schistosomiasis 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 the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6) and a 62 kDa fragment of myosin (Sj62), respectively.
In this study, we developed PDDV cocktails containing multiple epitopes of S. japonicum from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential in 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.
Our 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.
血吸虫病在流行国家仍然是一个主要的公共卫生问题，由三种主要血吸虫物种中的任何一种感染引起。尽管迄今为止尚无可用疫苗，但由于在一生中反复感染的个体可产生自然免疫力，因此该策略似乎可行。由于已证明引发Th1型和Th2型反应的疫苗接种均有助于产生保护性免疫，因此具有刺激免疫反应多个分支能力的疫苗制剂可能是最有效的。此前我们开发了基于单个Th细胞和B细胞表位的部分保护性肽-DNA双疫苗（PDDV）（分别为T3-PDDV和B3-PDDV），它们能够分别引发针对日本血吸虫22.6 kDa体表抗原（Sj22.6）和肌球蛋白62 kDa片段（Sj62）的免疫反应。
在本研究中，我们通过预测细胞毒性、辅助性和B细胞表位，开发了包含来自Sj22.6、Sj62和Sj97抗原的多个日本血吸虫表位的PDDV混合物，并在体内评估了疫苗潜力。结果显示，用单表位PDDV免疫的小鼠分别引发了Tc、Th或B细胞反应，用T3或B3单表位PDDV制剂免疫的小鼠对感染有部分保护作用。然而，用多组分（3种PDDV组分）制剂免疫的小鼠引发的免疫反应各不相同，其免疫保护作用不如单表位PDDV制剂。
我们的数据表明，与单独施用每种组分相比，组合这些不同抗原并未产生更有效的疫苗制剂，并且进一步表明，用抗原性不同的疫苗靶点进行免疫接种所导致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。
