Mucosal delivery of tuberculosis vaccines: a review of current approaches and challenges

Abstract

Introduction: Tuberculosis (TB) remains a major health threat and it is now clear that the current vaccine, BCG, is unable to arrest the global TB epidemic. A new vaccine is needed to either replace or boost BCG so that a better level of protection could be achieved. The route of entry of Mycobacterium tuberculosis, the causative organism, is via inhalation making TB primarily a respiratory disease. There is therefore good reason to hypothesize that a mucosally delivered vaccine against TB could be more effective than one delivered via the systemic route.Areas covered: This review summarizes the progress that has been made in the area of TB mucosal vaccines in the last few years. It highlights some of the strengths and shortcomings of the published evidence and aims to discuss immunological and practical considerations in the development of mucosal vaccines.Expert opinion: There is a growing body of evidence that the mucosal approach to vaccination against TB is feasible and should be pursued. However, further key studies are necessary to both improve our understanding of the protective immune mechanisms operating in the mucosa and the technical aspects of aerosolized delivery, before such a vaccine could become a feasible, deployable strategy.

Keywords: Tuberculosis; aerosol; challenges; delivery; mucosal; vaccination.

Figure 1.

Respiratory mucosal responses following M.tb infection or mucosal vaccination. DC = dendritic cells, EC = epithelial cells, sIgA = secreroty IgA, Brm = resident memory B cells, Trm = resident memory T cells, M.tb= Mycobacterium tuberculosis, iBALT = inducible bronchus-associated lymphoid tissue. Created with Biorender.com.

Figure 2.

Respiratory system in man and vaccine deposition following aerosol delivery (created with BioRender.com).