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. @ERSpublications Immunisation route determines TB vaccine efficacy based on whether T-cells can enter restricted lung mucosal sites http://ow.ly/M0shT

Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A

“…Further experiments, will address the ability of B–C–M to induce antigen specific memory responses and to provide durable protection when mice are challenged much later after vaccination. In addition, the distribution of antigen-specific T cells in different lung compartments will be further explored [37] .…”

Intranasal Vaccination with Mannosylated Chitosan Formulated DNA Vaccine Enables Robust IgA and Cellular Response Induction in the Lungs of Mice and Improves Protection against Pulmonary Mycobacterial Challenge

“…Modulation of immunity, especially manipulating antigens to be more efficiently presented by antigen-presenting cells (APCs) that can activate the effector T and B cells of the immune defense is a major goal in treatment and prevention of bacterial or viral infections (Lai et al, 2015 ). The respiratory tract is the portal of entry for M.tb (Rodriguez et al).…”

BCG vaccination for bovine tuberculosis; conclusions from the Jerusalem One Health workshop

“…Although human BCG today is primarily administered through the intradermal route, oral BCG administration has a long history and was used in multiple controlled studies performed in the 1920s and 1930s; demonstrating significant protection against TB (Aronson & Dannenberg, ; Kerszturi, ). More recent studies showed that oral BCG administration induces mucosal immunity, with enhanced TB‐specific secretory IgA, T‐cell homing to restricted lung mucosal compartments and bronchoalveolar lavage recovery of these T‐cells, compared to intradermal vaccination (Hoft et al., ; Lai, Afkhami, Haddadi, Jeyanathan, & Xing, ). In studies using rhesus macaques, pulmonary mucosal BCG vaccination conferred enhanced protection compared to standard intradermal BCG (Verreck et al., ), and it seems preferable to match the route of vaccination and natural infection (Manjaly & McShane, ).…”