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Navigating to the most promising directions amid complex fields of vaccine development: a chlamydial case study.
Expert Review of Vaccines ( IF 5.5 ) Pub Date : 2019-12-10 , DOI: 10.1080/14760584.2019.1698954
David Lizárraga 1, 2 , Scott Carver 1 , Peter Timms 2
Affiliation  

Background: Vaccine-development research is proliferating making it difficult to determine the most promising vaccine candidates. Exemplary of this problem is vaccine development against Chlamydia, a pathogen of global public health and financial importance.Methods: We systematically extracted data from studies that included chlamydial load or host immune parameter measurements, estimating 4,453 standardized effect sizes between control and chlamydial immunization experimental groups.Results: Chlamydial immunization studies most often used (78%) laboratory mouse models. Depending on chlamydial species, single and multiple recombinant protein, viral and bacterial vectors, dendritic transfer, and dead whole pathogen were most effective at reducing chlamydial load. Immunization-driven decrease in chlamydial load was associated with increases in IFNg, IgA, IgG1, and IgG2a. Using data from individual studies, the magnitude of IgA and IgG2a increase was correlated with chlamydial load reduction. IFNg also showed this pattern for C. trachomatis, but not for C. muridarum. We also reveal the chlamydial vaccine development field to be highly bias toward studies showing these effects, limiting lessons learned from negative results.Conclusions: Most murine immunizations against Chlamydia reduced chlamydial load and increased host immune parameters. These methods are novel for vaccine development and are critical in identifying trends where large quantities of literature exist.

中文翻译:

在疫苗开发的复杂领域中导航到最有希望的方向:衣原体案例研究。

背景:疫苗开发研究激增,难以确定最有希望的候选疫苗。方法:我们系统地从包括衣原体载量或宿主免疫参数测量在内的研究中提取数据,估计对照和衣原体免疫实验组之间的4,453个标准化效应大小结果:衣原体免疫研究最常使用(78%)实验室小鼠模型。根据衣原体物种的不同,单个和多个重组蛋白,病毒和细菌载体,树突状转移以及完全死亡的病原体在减少衣原体负荷方面最有效。免疫驱动的衣原体负荷减少与IFNg的增加有关,IgA,IgG1和IgG2a。使用个别研究的数据,IgA和IgG2a的增加与衣原体负荷减少相关。IFNg对于沙眼衣原体也显示出这种模式,但对muridarum不存在。我们还揭示了衣原体疫苗的开发领域对显示这些作用的研究具有高度偏向性,从而限制了从阴性结果中学到的经验教训。结论:大多数针对衣原体的小鼠免疫接种可降低衣原体载量并增加宿主免疫参数。这些方法对于疫苗开发是新颖的,并且对于确定存在大量文献的趋势至关重要。我们还揭示了衣原体疫苗的开发领域对显示这些作用的研究具有高度偏向性,从而限制了从阴性结果中学到的经验教训。结论:大多数针对衣原体的小鼠免疫接种可降低衣原体载量并增加宿主免疫参数。这些方法对于疫苗开发是新颖的,并且对于确定存在大量文献的趋势至关重要。我们还揭示了衣原体疫苗的开发领域对显示这些作用的研究具有高度偏向性,从而限制了从阴性结果中学到的经验教训。结论:大多数针对衣原体的小鼠免疫接种可降低衣原体载量并增加宿主免疫参数。这些方法对于疫苗开发是新颖的,并且对于识别存在大量文献的趋势至关重要。
更新日期:2019-11-01
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