Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

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.

Rotavirus vaccines: how they work or don't work

In 2004 and 2006, two new rotavirus vaccines – Rotarix™and RotaTeq™– were licensed worldwide. Both are live virus vaccines and are composed of either a monovalent attenuated human rotavirus or five bovine–human reassortant rotaviruses, respectively. Studies in humans and animals have reported correlations between rotavirus antibody levels and protection, the most consistent of which has been with rotavirus IgA. Cellular immunity was also found to have a role in protection after live rotavirus immunisation, particularly in mice. However, the primary importance of CD8+T cells may be in resolution of infection and that of CD4+T cells may be their helper function, particularly for antibody production. CD4+T cells have been reported to have a more direct role in protection after mucosal immunisation with non-living rotavirus vaccines, possibly because of direct or indirect effects of the cytokines they generate. Immune effectors have overlapping functions, and protection against rotavirus by either live or non-living vaccines is probably enhanced by this redundancy.