Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection.
Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection.
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DOI：
10.12688/wellcomeopenres.15487.1
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发表时间：
2019-01-01
影响因子：
--
通讯作者：
Wright, Gavin J
中科院分区：
文献类型：
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作者：
Crosnier, Cecile;Brandt, Cordelia;Wright, Gavin J
背景：血吸虫病是影响热带和热带地区人群的一种主要寄生虫病。已有78个国家报告了这种寄生虫的传播，在流行地区造成严重发病率和每年约20万人死亡。目前对该病的管理办法是对有感染风险的人群大量使用吡喹酮；然而，对单一药物的依赖增加了寄生虫对唯一广泛可用的治疗方法产生耐药性的可能性。开发一种有效的疫苗将是一种更有力的控制方法，但目前还没有这种方法，因此，确定能够引起保护性免疫反应的新免疫原仍然是一个优先事项。由于寄生虫生命周期的复杂性，确定新的候选疫苗主要依赖于使用动物模型和一组有限的重组蛋白。方法：在本研究中，我们建立了在小鼠中测试大量候选疫苗的基础设施，并利用它筛选了96种来自曼氏血吸虫的细胞表面和分泌重组蛋白。这种方法使用标准化免疫和经皮感染方案，使我们能够以系统的方式比较广泛的抗原集。结果：尽管在最初的筛选中，一些候选疫苗与卵子数量的统计学显著减少有关，但这些观察结果不能在随后的挑战中重复，而且所研究的蛋白质中没有一种与抗感染的强烈保护作用有关。结论：虽然在我们的疫苗接种方案中没有抗原单独诱导可重复的和强烈的保护作用，但我们已经建立了实验基础设施，以便在小鼠感染模型中进行大规模系统的血吸虫病亚单位疫苗试验。
Background: Schistosomiasis is a major parasitic disease affecting people living in tropical and sup-tropical areas. Transmission of the parasite has been reported in 78 countries, causing significant morbidity and around 200,000 deaths per year in endemic regions. The disease is currently managed by the mass-administration of praziquantel to populations at risk of infection; however, the reliance on a single drug raises the prospect of parasite resistance to the only treatment widely available. The development of an effective vaccine would be a more powerful method of control, but none currently exists and the identification of new immunogens that can elicit protective immune responses therefore remains a priority. Because of the complex nature of the parasite life cycle, identification of new vaccine candidates has mostly relied on the use of animal models and on a limited set of recombinant proteins. Methods: In this study, we have established an infrastructure for testing a large number of vaccine candidates in mice and used it to screen 96 cell-surface and secreted recombinant proteins from Schistosoma mansoni. This approach, using standardised immunisation and percutaneous infection protocols, allowed us to compare an extensive set of antigens in a systematic manner. Results: Although some vaccine candidates were associated with a statistically significant reduction in the number of eggs in the initial screens, these observations could not be repeated in subsequent challenges and none of the proteins studied were associated with a strongly protective effect against infection. Conclusions: Although no antigens individually induced reproducible and strongly protective effects using our vaccination regime, we have established the experimental infrastructures to facilitate large-scale systematic subunit vaccine testing for schistosomiasis in a murine infection model.