Pilla Giulia, Wu Tao, Grassel Christen, Moon Jonathan, Foulke-Abel Jennifer, Tang Christoph M, Barry Eileen M
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1509, USA.
Pathogens. 2021 Aug 25;10(9):1079. doi: 10.3390/pathogens10091079.
is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low-middle income countries. prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in is the development of effective vaccines. There is no licensed vaccine against and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic . The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type . These promising results highlight the utility of enteroids as an innovative preclinical model to evaluate vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen.
是全球细菌性痢疾的主要病因，在中低收入国家导致高死亡率，尤其是五岁以下儿童。在高收入国家流行，且在工业化国家也日益普遍，在这些国家出现了多重耐药菌株，成为重大公共卫生问题。对抗耐药性的一种策略是开发有效的疫苗。目前尚无针对的许可疫苗，且由于缺乏有效的小动物模型，疫苗开发受到阻碍。在这项工作中，我们首次使用人肠类器官作为模型系统，评估质粒稳定的减毒活疫苗菌株CVD 1233 - SP，以及表达产肠毒素抗原的多价衍生物CVD 1233 - SP::CS2 - CS3。还在豚鼠模型中测试了这些菌株的免疫原性和保护能力，证明它们能够引发血清和粘膜抗体反应，以及对野生型攻击的保护作用。这些有前景的结果突出了肠类器官作为评估疫苗候选物的创新临床前模型的实用性，为针对这种重要人类病原体的预防策略的开发取得了重大进展。
