The Common Mucosal System Fifty Years on: From Cell Traffic in the Rabbit to Immune Resilience to SARS-CoV-2 Infection by Shifting Risk within Normal and Disease Populations

The idea of a common mucosal immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential to modulate the impact of vaccination-induced protection against infection of the airway has been poorly understood. The consequent failure of the current SARS-CoV-2 vaccination to satisfy expectations with respect to prevention of infection, viral transmission, duration of protection, and pattern of clinical protection, led to public health and medical decisions now under review. This review summarises knowledge of the CMS in man, including the powerful role it plays in immune protection and lessons with respect to what can and cannot be achieved by systemic and mucosal vaccination for the prevention of airway infection. The powerful impact in both health and disease of optimising delivery of immune protection using selected isolates from the respiratory microbiome is demonstrated through a review of randomised controlled trials (RCTs) in subjects with chronic airway disease, and in otherwise healthy individuals with risk factors, in whom the idea of mucosal immune resilience is introduced. This review is dedicated to two giants of mucosal immunology: Professors John Bienenstock and Allan Cripps. Their recent deaths are keenly felt by their colleagues and students.