Per Os to Protection – Targeting the Oral Route to Enhance Immune-mediated Protection from Disease of the Human Newborn

Insight into the mechanisms that guide the host immune response towards either immunogenicity or tolerance is crucial for the success of many biomedical interventions, including vaccination. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 In this regard, early life is of particular interest as young infants not only suffer the highest burden of infectious disease across the human lifespan, but also receive the highest number of vaccinations.11, 12, 13, 14 Vaccines preventing infections or disease are amongst the most cost-effective life-saving medical interventions in history.15 The young (<2 years of age), including newborns, receive most of the vaccines given globally.16 For example, the World Health Organization (WHO) Expanded Program on Immunization (EPI) recommends up to 9 different types of vaccines (e.g. live attenuated, subunit, adjuvanted etc.) in the first 2 years of life, but only 4 and 3 to adolescents and adults, respectively; and between 21–24 doses of vaccines are recommended for children under 2 years of age, vs. only 7 for adolescents and 5 for adults.17 In this Perspective, we highlight how the uniqueness of orally (per os (p.o.) = by mouth) induced immunity in early life offers highly promising approaches to enhance immune-mediated protection at the start of life. The oral route also presents a more feasible thus scalable approach to public health interventions, especially in resource constrained settings.18, 19, 20, 21 An increased focus on investigating p.o. administration of immune modulating interventions (e.g. vaccines) thus appears prudent.