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
• vaccination
• mucosal
• aerosol
• delivery
• challenges

Article highlights

• Matching the route of infection with the route of vaccination is an attractive approach for the development of vaccines against TB.

• A number of successful mucosal vaccines against other diseases support the feasibility of this route for vaccination

• An increasing body of evidence in rodents, non-human primates, and humans highlight the immunogenicity and safety of mucosal TB vaccines.

• Better understanding of innate and adaptive immune responses against M.tb in the mucosa is required

• Future research should address the remaining key challenges, namely vaccine aerosolization, dosing and distribution within the respiratory mucosa

Acknowledgments

H McShane and R Reljic co-chair the 'Aerosol Research Community’ at the Collaboration for TB Vaccine Discovery (CTVD). R Reljic and M J Paul received support from the H2020 EC grant 643558 awarded to the EMI-TB Consortium. E Stylianou and H McSane received support from the European Union's Horizon 2020 research and innovation program under grant agreement no. 643381. H McShane is a Wellcome Trust Investigator (WT 206331/Z/17/Z).

Declaration of interest

E Stylianou has received support from the European Union's Horizon 2020 research and innovation program under grant agreement no. 643381. H McShane is a Wellcome Trust Investigator (WT 206331/Z/17/Z) and from European Union's Horizon 2020 research and innovation program under grant agreement no. 643381. M J Paul and R Reljic have received support from the H2020 EC grant 643558 awarded to the EMI-TB Consortium. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.