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تسجيل

Mucosal Tolerance and Oral Vaccines

المؤلف:  Abbas, A. K., Lichtman, A. H., Pillai, S., & Henrickson, S. E.

المصدر:  Cellular and Molecular Immunology (2026)

الجزء والصفحة:  11E, P332

2026-10-07

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Mucosal tolerance is systemic unresponsiveness to antigens that are ingested or otherwise administered via mucosal tis sues. Mucosal tolerance induced by ingestion of antigens, called oral tolerance, has been most clearly demonstrated in experimental rodent models. Mice fed high doses of a protein antigen may subsequently show impaired humoral and T cell–mediated responses to the same antigen administered by other routes, such as through the skin. A similar phenomenon can be demonstrated when antigens are administered through the nasal passages into the respiratory mucosa, and the more general term mucosal tolerance is used to describe tolerance induced by oral or nasal antigen administration. The physiologic role of oral tolerance is speculated to be the prevention of potentially harmful immune responses to food proteins and commensal bacteria. The underlying mechanisms of oral tolerance are not well understood but likely include the mechanisms of peripheral tolerance discussed in Chapter 15, such as anergy, deletion, and Treg-mediated suppression. Oral tolerance is systemic because Tregs induced in mucosa may circulate to other tissues, or effector T cells may be rendered unresponsive in the gut and are no longer able to respond to antigens at other sites. Attempts to treat autoimmune disease by oral or nasal administration of relevant self antigens have been unsuccessful, but there has been success in reducing the development of peanut allergy by oral administration of peanut extract during early childhood. Furthermore, feeding allergenic foods early in life can forestall allergy in some susceptible patients.

Oral administration of antigens in the setting of concomitant stimulation of innate immunity can lead to productive adaptive immune responses. The first oral vaccine developed was for polio, and now, oral vaccines are in use to protect against typhoid (caused by the bacterium S. typhi), cholera (caused by V. cholera), and rotavirus infection. In all these cases, the vaccine consists of an attenuated form of the microbe, which can trigger local innate immune responses. There is great interest in developing oral vac cines because of their ease of administration. Incorporating vac cine antigens in nonreplicating adenovirus vectors may increase the types of infections against which oral vaccines are feasible. In fact, promising results have been reported with such a vaccine for SARS-CoV-2, the cause of COVID-19.