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Combatting Tumours at the Gut With Novel Oral Vaccine Made by Bacteria Robot
A novel oral vaccine system developed using a sugar-controlled bacteria robot may be used as an antigen delivery and display platform that can prevent a variety of diseases.

A recent study led by Professor Nie Guangjun and Professor Zhao Xiao at the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences has successfully demonstrated that orally administered bacteria can be used as an effective vaccine vehicle to secrete small membrane vesicles in the gut to target various tumours of animal models.

Compared to vaccines administered via injections, oral vaccines are much easier to take and are generally cheaper. They are also able to activate the body’s adaptive immune response by stimulating immune cells in the intestine, the largest immune organ (hence a stronger immune response). Unfortunately, clinical uses of oral vaccines, particularly for oral tumour vaccines, remain limited due to the harsh environment of the digestive tract and the complex intestinal epithelial barriers that prevent successful delivery.

To overcome these obstacles, the researchers have developed an oral sugar-controlled bacteria robot that can produce tumour vaccine in the gut. By genetically engineering E. coli, the team designed a bacteria robot that can secrete outer membrane vesicles (OMVs) that carry tumour antigens under the induction of arabinose, a five-carbon sugar found commonly in nature.

“Initially, a report of bacterial enteritis by food contamination came to our attention. If pathogenic bacteria can break through biological barriers and provoke an immune response, artificially engineered bacteria should be able to overcome the complex gastrointestinal environment. Inspired by this hypothesis, we started to try to use bacterial robots to deliver oral vaccines,” said Prof. Zhao. “However, bacteria are too large to penetrate the thick mucus layer and intestinal epithelial barrier to reach the immune cells at lamina propria. Fortunately, numerous studies have demonstrated that OMVs released by intestinal bacteria are involved in the immune regulation of the body.”

Since OMVs are natural mediators for the interaction between the gut microbiota and the body’s immune system, OMVs can act together with tumour antigens to penetrate the intestinal mucus and epithelial barrier. They can then be taken up by antigen-presenting cells in the lamina propria, a special layer of the mucosa in the gut. In several preclinical tumour models, the oral vaccine was found to generate potent anti-tumour immune responses and immune memory effects.

“This work shows that this oral bacteria robot can controllably produce vaccines against multiple tumours in mice with the help of genetic engineering technology. What’s more, it can be used as an antigen delivery and display platform to prevent other disease[s] such as contagion. It holds great promise for further development of oral vaccines,” said Prof. Nie.

Source: Yue et al. (2022). Antigen-bearing outer membrane vesicles as tumour vaccines produced in situ by ingested genetically engineered bacteria. Nature Biomedical Engineering.

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