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 world wide with mucosal membranes being the most frequent portals of entry of pat hogenic micro-organisms. This has prompted studies aimed at the development of vaccination protocols that would lead to an increased protection of muc osae through an understanding of the common mucosal immune system as an imm une communication network between mucosal sites. Recent studies have sugges ted that preferential subnetworks 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 respira tory tract and middle ear. Mucosal immunization with whole formalin killed Pseudomonas aeruginosa (Pa), Branhamella catarrhalis, nontypable Haemophilu s influenzae (NTHi) or Streptococcus pneumoniae (Spn) results in enhanced h omologous bacterial clearance from the lung of immune animals challenged wi th 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 opsonis ing antibody, antigen specific CD4+ T helper cells, cytokine responses and recruitment of activated polymophonuclear neutrophils. The mechanisms induc ed by immunization which stimulates the immune system to rapidly mobilise b oth innate and specific immune responses during infection are the subject o f ongoing research. (C) 1999 Elsevier Science Ltd. All rights reserved.