Confronting challenges to enterotoxigenic Escherichia coli vaccine development.
Confronting challenges to enterotoxigenic Escherichia coli vaccine development.
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DOI：
10.3389/fitd.2021.709907
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发表时间：
2021-01-01
期刊：
影响因子：
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通讯作者：
Fleckenstein, James M
中科院分区：
文献类型：
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作者：
Fleckenstein, James M
产肠毒素大肠杆菌（ETEC）是大肠杆菌的一种具有遗传可塑性的致病变种。大肠杆菌，定义为产生热不稳定（LT）和热稳定（ST）肠毒素。40多年前，这些病原体在出现严重霍乱样腹泻的患者中被认识到，现在已知每年导致数亿例有症状的感染。世界上中低收入地区的儿童无法获得清洁水和基本卫生设施，受到ETEC的影响尤为严重。除了急性腹泻病外，这些病原体仍然是五岁以下儿童死亡的一个重要原因，并一再与儿童营养不良和发育迟缓的后遗症有关。因此，可以预防ETEC感染的疫苗仍然是一个高度优先事项。尽管经过几十年的努力，一种获得许可的疫苗，以防止这些病原体的广度仍然是一个令人向往的目标，和潜在的遗传可塑性的E。大肠杆菌中的ETEC对疫苗的开发提出了根本性的挑战，该疫苗可以涵盖ETEC的完整抗原谱。然而，新的策略，包括类毒素，更完整的了解ETEC的分子发病机制，靶免疫原的结构细节，并发现更高度保守的毒力所必需的抗原，应加速进展，使广泛的保护性疫苗可行。
The enterotoxigenic Escherichia coli (ETEC) are a diverse and genetically plastic pathologic variant (pathovar) of E. coli defined by their production of heat-labile (LT) and heat-stable (ST) enterotoxins. These pathogens, which came to recognition more than four decades ago in patients presenting with severe cholera-like diarrhea, are now known to cause hundreds of millions of cases of symptomatic infection annually. Children in low-middle income regions of the world lacking access to clean water and basic sanitation are disproportionately affected by ETEC. In addition to acute diarrheal morbidity, these pathogens remain a significant cause of mortality in children under the age of five years and have also been linked repeatedly to sequelae of childhood malnutrition and growth stunting. Vaccines that could prevent ETEC infections therefore remain a high priority. Despite several decades of effort, a licensed vaccine that protects against the breadth of these pathogens remains an aspirational goal, and the underlying genetic plasticity of E. coli has posed a fundamental challenge to development of a vaccine that can encompass the complete antigenic spectrum of ETEC. Nevertheless, novel strategies that include toxoids, a more complete understanding of ETEC molecular pathogenesis, structural details of target immunogens, and the discovery of more highly conserved antigens essential for virulence should accelerate progress and make a broadly protective vaccine feasible.