The body’s mucosal membranes are highly susceptible to infection and have evolved uniquely powerful defense mechanisms. Oral vaccines leverage the mucosal immune system to halt infectious diseases before they can cause illness.
Download this poster from Drug Discovery News to learn how oral vaccines navigate the digestive system, trigger an adaptive immune response, and create a barrier against pathogen infiltration, ultimately eliminating pathogens and preventing infection spread.
Oral vaccines stop pathogens in their tracks before they get a chance to cause disease.
By Luisa Torres, PhD
Illustrations by Janette Lee-Latour
A mouthful of benefits
For those daunted by the sharp sting of needles, oral vaccines offer an alternative route to immunity. Oral vaccines leverage the body's mucosal surfaces, such as those in the digestive tract, as battlegrounds to neutralize harmful pathogens before they can infiltrate the bloodstream and wreak havoc on other tissues (1). This process, known as mucosal immunity, gives oral vaccines a distinct edge in the ongoing battle against infectious diseases.
Surviving the digestive system
To elicit mucosal immunity, oral vaccines must first survive the low pH of the stomach. The oral poliovirus vaccine, for instance, contains a weakened version of the poliovirus that resists stomach acidity and digestive enzymes due to having no lipid envelope that gastric enzymes can disrupt (2). Once it survives the stomach, the virus replicates primarily in the small intestine.
Hacking into the intestinal immune system
The virus passes the protective cell barrier of the small intestine by attaching to microfold cells, specialized epithelial cells that line the inner surface of the small intestine (3). Within the small intestine, the virus replicates, attracting dendritic cells (DCs) (4).
Generating adaptive immunity
An adaptive immune response ensues, which prepares the recipient for a future viral infection. DCs capture the virus and break down its viral proteins into fragments that they present to T cells (5). In response, T cells release cytokines to stimulate B cells to become plasma cells, prompting the secretion of IgA antibodies against the viral antigens (6).
Preventing infection spread
IgA antibodies integrate into the protective mucosal layer covering the epithelial cell barrier. If the active virus infects the host, IgA antibodies trap the virus in mucus and neutralize it (7). This prevents the virus from attacking other tissues and limits the replication and spread of the pathogen.
Eliminating pathogens
The gut’s muscle movements guide the virus-filled mucus blobs down the digestive tract. This material transforms into fecal matter in the colon and is ultimately expelled from the body (8).
The upper hand
Unlike systemic immunity, which primarily targets pathogens once they have invaded tissues, mucosal immunity neutralizes pathogens at the mucosal surfaces where they first enter the body, such as the digestive, respiratory, and urogenital systems (9). Oral vaccines mimic the natural route of infection for many pathogens, enabling the immune system to mount a fast response at the site of entry (10).
References
1. Zhu, Q. & Berzofsky, J. A. Oral vaccines: directed safe passage to the front line of defense. Gut microbes 4, 246–252 (2013).
2. Pfeiffer, J.K. Innate host barriers to viral trafficking and population diversity: lessons learned from poliovirus. Advances in virus research 77, 85-118 (2010).
3. Dillon, A. & Lo, D.D. M Cells: intelligent engineering of mucosal immune surveillance. Frontiers in Immunology 10, 1499 (2019).
4. Wang, M., Gao, Z., Zhang, Z., Pan, L., & Zhang, Y. Roles of M cells in infection and mucosal vaccines. Human vaccines & immunotherapeutics 10, 3544-51 (2014).
5. Mihret, A. The role of dendritic cells in mycobacterium tuberculosis infection. Virulence 3, 654-9 (2012).
6. Nizard, M., Diniz, M. O., Roussel, H., Tran, T., Ferreira, L. C. et al. Mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites. Human Vaccines & Immunotherapeutics 10, 2175-87 (2014).
7. Mantis, N., Rol, N., & Corthésy, B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 4, 603–611 (2011).
8. Connor, R.I. et al. Mucosal immunity to poliovirus. Mucosal Immunol 15, 1–9 (2022).
9. Vela Ramirez, J.E, Sharpe, L.A., & Peppas, N.E. Current state and challenges in developing an oral vaccine. Adv Drug Deliv Rev 114, 116-131 (2017).
10. Długosz E. & Wesołowska A. Immune response of the host and vaccine development. Pathogens 12, 637 (2012).