预防性免疫幽门螺杆菌感染的孢子载体疫苗。

Prophylactic immunization to Helicobacter pylori infection using spore vectored vaccines.

机构信息

Department of Biological Sciences, Royal Holloway University of London, Egham, UK.

Institute of Biotechnology and Environment, Nha Trang University, Nha Trang, Vietnam.

出版信息

Helicobacter. 2023 Aug;28(4):e12997. doi: 10.1111/hel.12997. Epub 2023 Jun 14.

Abstract

BACKGROUND

Helicobacter pylori infection remains a major public health threat leading to gastrointestinal illness and increased risk of gastric cancer. Mostly affecting populations in developing countries no vaccines are yet available and the disease is controlled by antimicrobials which, in turn, are driving the emergence of AMR.

MATERIALS AND METHODS

We have engineered spores of Bacillus subtilis to display putative H. pylori protective antigens, urease subunit A (UreA) and subunit B (UreB) on the spore surface. Following oral dosing of mice with these spores, we evaluated immunity and colonization in animals challenged with H. pylori.

RESULTS

Oral immunization with spores expressing either UreA or UreB showed antigen-specific mucosal responses (fecal sIgA) including seroconversion and hyperimmunity. Following challenge, colonization by H. pylori was significantly reduced by up to 1-log.

CONCLUSIONS

This study demonstrates the utility of bacterial spores for mucosal vaccination to H. pylori infection. The heat stability and robustness of Bacillus spores coupled with their existing use as probiotics make them an attractive solution for either protection against H. pylori infection or potentially for therapy and control of active infection.

摘要

背景

幽门螺杆菌感染仍然是一个主要的公共卫生威胁,导致胃肠道疾病和胃癌风险增加。由于主要影响发展中国家的人群,目前还没有疫苗可用,该疾病通过抗生素控制,而抗生素又在推动抗生素耐药性的出现。

材料与方法

我们已经对枯草芽孢杆菌的孢子进行了工程改造,使其在孢子表面展示幽门螺杆菌的假定保护性抗原,包括脲酶亚单位 A(UreA)和亚单位 B(UreB)。在给小鼠口服这些孢子后,我们评估了动物在受到幽门螺杆菌挑战时的免疫和定植情况。

结果

用表达 UreA 或 UreB 的孢子进行口服免疫显示了抗原特异性黏膜反应(粪便 sIgA),包括血清转换和超免疫。在挑战后,幽门螺杆菌的定植减少了多达 1 个对数级。

结论

本研究证明了细菌孢子用于幽门螺杆菌感染黏膜接种的有效性。枯草芽孢杆菌孢子的热稳定性和稳健性,加上它们作为益生菌的现有用途,使它们成为预防幽门螺杆菌感染或潜在治疗和控制活跃感染的有吸引力的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e46c/10909515/4a554e6aaf64/HEL-28-e12997-g004.jpg

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