Compared with vaccination, oral vaccine is much easier to take, and mostly in a lower cost. More importantly, it activates the body’s adaptive immune response by stimulating the immune cells in the intestine which is the largest immune organ. Therefore, it is expected to generate strong immune responses. However, the oral vaccine system is still very limited. There are two major challenges for the development of oral tumor vaccine. One is the harsh environment in digestive tract and the other is the complex intestinal epithelial barriers.
To overcome these challenges, the researchers developed an oral sugar-controlled bacteria robot to produce tumor vaccine in the gut. They designed a bacteria robot based on the genetically engineered E. coli which can secrete outer membrane vesicles (OMVs) carrying tumor antigens under the induction of arabinose, a five-carbon sugar found widely in nature.
As a natural mediator for interaction between the gut microbiota and the body’s immune system, OMVs together with tumor antigens can effectively penetrate the intestinal mucus and epithelial barrier, and be taken up by antigen-presenting cells in lamina propria, one special layer of mucosa of the gut. Ultimately, the oral vaccine system activates strong antitumor immune responses and immune memory effects in multiple preclinical tumor models.
"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, artificial 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.”
"This work shows that this oral bacteria robot can controllably produce vaccines against multiple tumors 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 such as contagion. It holds great promise for further development of oral vaccines,” said Prof. NIE.
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