Tuberculosis vaccines: Opportunities and challenges

Abstract

Tuberculosis (TB) is a serious disease around the world. Bacillus Calmette-Guérin (BCG) is the only TB vaccine licensed for use in human beings, and is effective in protecting infants and children against severe miliary and meningeal TB. However, BCG's protective efficacy is variable in adults. Novel TB vaccine candidates being developed include whole-cell vaccines (recombinant BCG (rBCG), attenuated Mycobacterium tuberculosis, killed M. tuberculosis or Mycobacterium vaccae), adjuvanted protein subunit vaccines, viral vector-delivered subunit vaccines, plasmid DNA vaccines, RNA-based vaccines etc. At least 12 novel TB vaccine candidates are now in clinical trials, including killed M. vaccae, rBCG ΔureC::hly, adjuvanted fusion proteins M72 and H56 and viral vectored MVA85A. Unfortunately, in TB, there are no correlates of vaccine-induced protection, although cell-mediated immune responses such as interferon-gamma (IFN-γ) production are widely used to assess vaccine's immunogenicity. Recent studies suggested that central memory T cells and local secreted IgA correlated with protection against TB disease. Clinical TB vaccine efficacy trials should invest in identifying correlates of protection, and evaluate new TB biomarkers emerging from human and animal studies. Accumulating new knowledge on M. tuberculosis antigens and immune profiles correlating with protection or disease risk will be of great help in designing next generation of TB vaccines.

Contemporary Concise Review 2018: Respiratory infections and tuberculosis

“…Novel TB vaccine candidates being developed include whole‐cell vaccines, adjuvanted protein subunit vaccines, viral vector‐delivered subunit vaccines, plasmid DNA vaccines, RNA‐based vaccines etc . Vaccines are useful as a first‐line tool in controlling infectious diseases because they are more readily applied on a population scale .…”

“…However, with the high global burden of latent TB Infection, vaccines capable of preventing pulmonary TB in infected individuals will be needed to reduce TB incidence quickly . At least 12 novel TB vaccine candidates are now in clinical trials . A subunit vaccine, M72/AS01E, showed 54% protection against active pulmonary TB in HIV‐negative adults with a positive IGRA in a recent phase IIb trial .…”

Immunological association of inducible bronchus-associated lymphoid tissue organogenesis in Ag85B-rHPIV2 vaccine-induced anti-tuberculosis mucosal immune responses in mice

“…In the present study, we found that organogenesis of iBALT contributed to the induction of Ag85B-specific immune responses, such as IFNγ and IgA antibody production in the lung, both of which are likely to be important arms of the protection against tuberculosis ( 35–37 ). iBALT organogenesis was induced by inoculation with null-HPIV2 vector, without the expression of Ag85B.…”

Towards new TB vaccines

“…Due to the difficulties in identifying antigens capable of generating a protective response, whole cell derived vaccines have gained increasing interest [212]. Whilst advantages with whole cell vaccines include a comprehensive antigen repertoire and similarity to natural infection [213], there are worries that this may simply induce a similarly semi-effectual immune response to that seen with natural M. tuberculosis infection [212].…”