title: Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments.
abstract: Despite the use of bacille Calmette-Guérin (BCG) for almost a century, pulmonary tuberculosis (TB) continues to be a serious global health concern. Therefore, there has been a pressing need for the development of new booster vaccines to enhance existing BCG-induced immunity. Protection following mucosal intranasal immunisation with AdHu5Ag85A is associated with the localisation of antigen-specific T-cells to the lung airway. However, parenteral intramuscular immunisation is unable to provide protection despite the apparent presence of antigen-specific T-cells in the lung interstitium. Recent advances in intravascular staining have allowed us to reassess the previously established T-cell distribution profile and its relationship with the observed differential protection. Respiratory mucosal immunisation empowers T-cells to home to both the lung interstitium and the airway lumen, whereas intramuscular immunisation-activated T-cells are largely trapped within the pulmonary vasculature, unable to populate the lung interstitium and airway. Given the mounting evidence supporting the safety and enhanced efficacy of respiratory mucosal immunisation over the traditional parenteral immunisation route, a greater effort should be made to clinically develop respiratory mucosal-deliverable TB vaccines.
authors.affiliation: McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, and Dept of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Rocky
authors.initials: R
authors.lastname: Lai
authors.affiliation: McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, and Dept of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Afkhami
authors.affiliation: McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, and Dept of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Siamak
authors.initials: S
authors.lastname: Haddadi
authors.affiliation: McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, and Dept of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Mangalakumari
authors.initials: M
authors.lastname: Jeyanathan
authors.affiliation: McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, and Dept of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada xingz@mcmaster.ca.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002634:Chemotaxis, Leukocyte; D054884:Host-Pathogen Interactions; D006801:Humans; D018928:Immunity, Mucosal; D007114:Immunization; D018836:Inflammation Mediators / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D016896:Treatment Outcome; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D018836:Inflammation Mediators; D032581:Tuberculosis Vaccines