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Oral Biologic Delivery: Advances Towards Oral Subunit, DNA and mRNA Vaccines and the Potential for Mass Vaccination During Pandemics.

Oral vaccination offers the promise of convenient, pain-free and self-administrable vaccine delivery. This is highly attractive in response to pandemic outbreaks where rapid mass vaccination is critical. Furthermore, oral vaccination produces mucosal, as well as systemic, immune responses, which protect against infection at mucosal surfaces. As the majority of pathogens enter the body through mucosal surfaces this may further enhance protection and minimize the spread of disease. The gastrointestinal (GI) tract presents a number of prospective mucosal inductive sites for targeting orally delivered vaccines, including the oral cavity, stomach and small intestine. Despite this, currently available oral vaccines are effectively limited to either live attenuated and inactivated vaccines against enteric diseases. The GI tract poses a number of challenges to the delivery of subunit and nucleic acid vaccines, including degradative processes that digest biologics and mucosal barriers that limit their absorption. This review summarizes the approaches currently under development and future opportunities for oral vaccine delivery to established (intestinal) and relatively new (oral cavity, stomach) mucosal targets. Special consideration is given to recent significant advances in oral biologic delivery that offer promise as future platforms for administration of oral vaccines. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.