By Pasha Yuen
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Oral Vaccines
When talking about vaccines, the first thing that comes to your mind may be getting an injection. However, some vaccines can be administered through an oral route instead. There are currently oral vaccines available to protect against several serious conditions including poliomyelitis (“polio”), cholera, rotavirus, and typhoid.
There are many advantages of oral administration compared with injection for vaccination. These include ease of administration without the use of needles, which requires less training for the healthcare providers and also reduces cost; no risk of injection site reactions; easier storage, since many injectable vaccines need to be stored at a low temperature; and speed, as oral vaccines can be quickly administered, which means more people can be vaccinated in each clinic.
The first oral vaccine proven to be effective was the oral polio vaccine (OPV). In the UK Polio vaccines are normally administered as injections to babies as part of the 6-in-1 vaccine, 4-in-1 (DTaP/IPV) pre-school booster, and the 3-in-1 (Td/IPV) teenage booster. Although there are no confirmed cases of polio infection in the UK since 1984, it is important to continue to immunise against this devastating condition to prevent another outbreak. Up to 75% of cases are asymptomatic, making polio extremely contagious, with 1 in 200 infections leading to irreversible paralysis. Between 5-10% of those paralysed die due to their breathing muscles becoming immobilised. Vaccinations have ensured that polio is mostly eradicated worldwide, following a global effort led by the World Health Organization, however there are still pockets of this virus in some regions of the world. As described in the first blog of this series, herd immunity can protect those who are unvaccinated, including those who are unable to receive vaccines due to specific health conditions that affect the immune system.
The UK NHS immunisation programme also includes 2 doses of oral rotavirus vaccine for all infants at 8 and 12 weeks old, except those who have severe combined immunodeficiency (SCID). This protects children from rotavirus, a highly transmissible pathogen that can cause diarrhoea and vomiting, which can be severe and even life-threatening in children. (Rotavirus vaccine – NHS [www.nhs.uk])
How does oral vaccination work?
Oral vaccines are swallowed, therefore they are administered directly into the gastrointestinal (GI) tract, targeting the gut-associated lymphoid tissue (GALT). This triggers a gut-based mucosal immune response.
Immunity in the gut is managed by dendritic cells and specialised M cells, which capture antigens and present them to the T cells for the subsequent immunity cascade. This cascade includes T cell and B cell differentiation, followed by generation of Immunoglobulin A (IgA). Secretory IgA is the type of antibody found in mucous secretions, which protects the body from pathogens entering via the gut (such as polio, rotavirus etc). Injection-based vaccines induce the production of IgG, which is responsible for a systemic (throughout the body and in the bloodstream) immune response rather than locally in the gut. Therefore, oral vaccines are needed where a specific gut protective effect is required. Secretory IgA in GALT is particularly important, due to its ability to block pathogens from adhering to mucosal surfaces.
Oral Vaccines – Challenges and Clinical Trials
Not everyone can be vaccinated using the currently available oral vaccines. For example, the oral version may contain an inactivated version of the virus, which may mutate in the body and become active lower down in the gastrointestinal tract. This would not cause a problem for the vaccinated individual as they will have mounted the immune response by then. But people with immune system disorders, or with carers who are not immune to the condition, may require a killed version of the virus, or an injection with specific parts of the pathogen. This is why some injectable versions are still required despite the advantages of oral vaccines.
Administration of vaccines through the oral route in general have a lower bioavailability, due to the degradation of antigens when entering the stomach and the intestine. Therefore, some of the obstacles in designing an oral vaccine include the resistance against the highly acidic environment in the stomach and the effect of digestion, which require having a higher level of antigens. In current years, efforts are still being made to improve the effectiveness and safety of currently available oral vaccines, for example a novel OPV clinical trial in Panama. (Study Details | Study of a Novel Type 3 Oral Poliomyelitis Vaccine in Panama | ClinicalTrials.gov)
In addition to the already available oral vaccines, clinical trials investigating oral vaccines against other pathogens are also taking place. A Phase II study completed in 2018 investigated the efficacy of oral H1N1-based influenza vaccine, which showed a promising result in terms of efficacy and safety. (Efficacy, immunogenicity, and safety of an oral influenza vaccine: a placebo-controlled and active-controlled phase 2 human challenge study – PubMed (nih.gov))
In the future, development of effective oral vaccines could be incredibly helpful in healthcare. Want to learn more on vaccination? Read the next blog in this series on seasonal vaccines!
Reference
Recent development of oral vaccines (Review) – PMC (nih.gov)
Oral Vaccines: A Better Future of Immunization – PMC (nih.gov)
