A vaccine is a biologic that improves immunity to disease. Vaccination is considered the most effective means of controlling infectious disease-related morbidity and mortality. Vaccination prevents over 2.5 million child deaths each year, globally, according to the World Health Organization (WHO).1
Half of the top ten leading causes of death in low-income countries are caused by infectious diseases including lower respiratory infections (e.g. COVID-19 and other causes of pneumonia), human immunodeficiency virus (HIV), diarrheal disease, malaria, and tuberculosis.2 Some prevalent pathogens including HIV lack an effective vaccine, however, an estimated 20% of prevalent pathogen-induced deaths result from vaccine-preventable diseases. Furthermore, this problem is not limited to low-income countries, COVID-19 is a top-three cause of death in the United States, despite the availability of vaccines.3 This indicates an unmet medical need to improve vaccine compliance rates and accessibility.
Vaccines are typically delivered via subcutaneous (SC) or intramuscular (IM) injection. Dendritic cells (DCs), however, can be found in higher concentrations in other areas of the body, such as the upper layers of the skin (epidermis and dermis), nasal mucosa and the gastrointestinal (GI) tract. The oral formulation of vaccines is therefore an ideal solution for delivery to the GI tract.
The majority of vaccinations are administered to children. Oral vaccines potentially have several advantages over conventional subcutaneous or intramuscularly injected vaccines. Firstly, compliance with oral vaccination is much more straightforward than conventional vaccines, especially for children, requires less equipment (syringes, needles), does not require a health professional to administer, and oral vaccine distribution is simpler. Secondly, oral vaccination may be more effective, offering both mucosal immunity and cellular immunity in addition to conventional systemic antibody-mediated immunity.2
Oral vaccine technology does face several challenges posed by the digestive tract such as pH changes and digestive enzymes that can degrade the vaccine components. For an oral vaccine to be successful the following conditions must be met:
1) successful delivery of active antigen (or encoding DNA) to intestinal cells
2) antigen transport across the mucosal barrier
3) activation of antigen-presenting cells
Oral vaccines face one challenge, in particular, that is crucial to overcome. If the dose is not correct or the immune system is not sufficiently stimulated they can promote immune tolerance of the antigen, instead of the desired protective effect. The correct selection of immune-stimulating adjuvants is therefore crucial for the success of oral vaccines.4
Oral vaccines represent around a quarter, US $14.91 billion, of the total vaccine market, worth US $61.04 billion in 2021 (Figure 1). The North American vaccine market alone is reportedly worth US $29.43 billion. Vaccines delivered by syringe, microneedle and nasal spray represent a share of around US $44.6922 billion, US $1.3220 billion, and US $0.1158 billion respectively. Between 2022 to 2027 the oral vaccine market is expected to grow at a CAGR of 7.3%. The overall vaccine market is expected to grow at a similar rate of 10.20% between 2021-2028.
The oral vaccine market is currently dominated by formulations that target rotavirus, cholera, polio, and typhoid fever. All of these diseases initiate infections via the GI tract. Oral formulations of COVID-19 and Flu vaccines are also under development.
Figure 1: Vaccine market share in billion USD segmented by mode of delivery.