Therapeutic Vaccines for Tuberculosis: An Overview

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis is the world's deadliest bacterial infection, resulting in more than 1.4 million deaths annually. The emergence of drug-resistance to first-line antibiotic therapy poses a threat to successful treatment, and novel therapeutic options are required, particularly for drug-resistant tuberculosis. One modality emerging for TB treatment is therapeutic vaccination. As opposed to preventative vaccination - the aim of which is to prevent getting infected by M. tuberculosis or developing active tuberculosis, the purpose of therapeutic vaccination is as adjunctive treatment of TB or to prevent relapse following cure. Several candidate therapeutic vaccines, using killed whole-cell or live attenuated mycobacteria, mycobacterial fragments and viral vectored vaccines are in current clinical trials. Other modes of passive immunization, including monoclonal antibodies directed against M. tuberculosis antigens are in various pre-clinical stages of development. Here, we will discuss these various therapeutics and their proposed mechanisms of action. Although the full clinical utility of therapeutic vaccination for the treatment of tuberculosis is yet to be established, they hold potential as useful adjunct therapies.

Keywords: mRNA vaccine; monoclonal antibody; mycobacterium; prevention of recurrence; therapeutic vaccines; tuberculosis.

Figure 1

Overview of selected therapeutic TB vaccines in the clinical pipeline. The initial stages of TB infection involve inhalation of Mtb bacilli into the lung and phagocytosis by resident alveolar macrophages. The human immune system can contain or eliminate Mtb infection in the majority of cases, only a small proportion of exposed individuals go on to develop active tuberculosis. Therapeutic TB vaccines serve as immunotherapeutic adjuncts to chemotherapy and act through modulating host anti-TB immunity. These vaccines are either administrated to potentiate treatment during treatment of active disease (middle) or to prevent recurrence or relapse after standard treatment (right), or to prevent reactivation of latent tuberculosis to active tuberculosis (left). Vaccines that are being developed to improve treatment outcomes in active TB comprise M. vaccae, RUTI, MIP and AERAS-402. Vaccines that prevent relapse and reinfection include H56:IC31 and ID: GLA-SE subunit vaccines, RUTI, BCG, the recombinant BCG vaccine VPM1002 as well as MVA-85A. These candidates are currently in phase 2 or 3 clinical trials in TB patients during or after completion of treatment.