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Vaccine-mediated protection against Campylobacter-associated enteric disease.
Science Advances ( IF 11.7 ) Pub Date : 2020-06-24 , DOI: 10.1126/sciadv.aba4511
Benjamin K Quintel 1 , Kamm Prongay 2 , Anne D Lewis 2 , Hans-Peter Raué 3 , Sara Hendrickson 3 , Nicholas S Rhoades 4 , Ilhem Messaoudi 4 , Lina Gao 5, 6 , Mark K Slifka 3 , Ian J Amanna 1
Affiliation  

Campylobacter coli and Campylobacter jejuni are responsible for 400 million to 500 million cases of enteric disease each year and represent the most common cause of bacterial gastroenteritis worldwide. Despite its global importance, Campylobacter vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. Here, we describe a naturally occurring Campylobacter-associated diarrhea model in outdoor-housed rhesus macaques. Using this model, we developed novel next-generation H2O2-based Campylobacter vaccines that induced strong antibacterial antibodies to multiple Campylobacter proteins including flagellin and provided up to 83% protection against severe C. coli–associated diarrhea. Whole-genome sequencing of circulating Campylobacter strains revealed little to no homology within lipooligosaccharide or capsular polysaccharide loci with the Campylobacter vaccine strains used in these studies, indicating that vaccine-mediated immunity was not restricted to a single homologous serotype. Together, these results demonstrate an important advance in vaccine development and a new approach to reducing Campylobacter-associated enteric disease.



中文翻译:


疫苗介导的针对弯曲杆菌相关肠道疾病的保护。



大肠杆菌空肠弯曲菌每年造成 4 亿至 5 亿例肠道疾病,是全世界细菌性胃肠炎的最常见原因。尽管弯曲杆菌疫苗具有全球重要性,但由于缺乏能够概括人类疾病发病机制的动物模型,弯曲杆菌疫苗的开发受到了阻碍。在这里,我们描述了户外饲养的恒河猴中自然发生的弯曲杆菌相关腹泻模型。利用该模型,我们开发了新型下一代基于 H 2 O 2弯曲杆菌疫苗,该疫苗可诱导针对多种弯曲杆菌蛋白(包括鞭毛蛋白)的强抗菌抗体,并针对严重的大肠杆菌相关腹泻提供高达 83% 的保护。循环弯曲杆菌菌株的全基因组测序显示,脂寡糖或荚膜多糖基因座与这些研究中使用的弯曲杆菌疫苗株几乎没有同源性,表明疫苗介导的免疫并不限于单一同源血清型。总之,这些结果证明了疫苗开发的重要进展和减少弯曲杆菌相关肠道疾病的新方法。

更新日期:2020-06-25
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