Killed whole bacterial cells, a mucosal delivery system for the induction of immunity in the respiratory tract and middle ear: An overview

Infectious diseases remain a leading cause of morbidity and mortality worldwide with mucosal membranes being the most frequent portals of entry of pathogenic micro-organisms. This has prompted studies aimed at the development of vaccination protocols that would lead to an increased protection of mucosae through an understanding of the common mucosal immune system as an immune communication network between mucosal sites. Recent studies have suggested that preferential sub-networks exist within the system and these studies have exploited the gut-associated lymphoid tissue (GALT)-lung sub-network in the development of oral vaccine strategies for infections of the respiratory tract and middle ear. Mucosal immunization with whole formalin killed Pseudomonas aeruginosa (Pa), Branhamella catarrhalis, nontypable Haemophilus influenzae (NTHi) or Streptococcus pneumoniae (Spn) results in enhanced homologous bacterial clearance from the lung of immune animals challenged with live bacteria. These studies have been extended to the middle ear where similar results have been observed for NTHi and Spn. Mechanisms responsible for inducing enhanced bacterial clearance from the airways include opsonising antibody, antigen specific CD4+ T helper cells, cytokine responses and recruitment of activated polymophonuclear neutrophils. The mechanisms induced by immunization which stimulates the immune system to rapidly mobilise both innate and specific immune responses during infection are the subject of ongoing research.