Human Biomarkers: Can they help us to Develop a new Tuberculosis Vaccine?

Abstract

The most effective intervention for the control of infectious disease is vaccination. The BCG vaccine, the only licensed vaccine for the prevention of tuberculosis (TB) disease, is only partially effective and a new vaccine is urgently needed. Biomarkers can aid the development of new TB vaccines through discovery of immune mechanisms, early assessment of vaccine immunogenicity or vaccine take and identification of those at greatest risk of disease progression for recruitment into smaller, targeted efficacy trials. The ultimate goal, however, remains a biomarker of TB vaccine efficacy that can be used as a surrogate for a TB disease end point and there remains an urgent need for further research in this area.

Historical BCG vaccination combined with drug treatment enhances inhibition of mycobacterial growth ex vivo in human peripheral blood cells

“…In order for a novel TB vaccination strategy to be implemented, its efficacy needs to be demonstrated in large and expensive efficacy trials 17 . Recently, funders have become more reluctant to provide the required investment due to the risk of failure 18 . As there are currently at least a dozen of TB vaccine candidates in the clinical trial pipeline and more candidates under pre-clinical development 19 , an effort to screen these candidates at early phases is needed to prioritise which candidates should be tested with the available funding and field sites.…”

The in vitro direct mycobacterial growth inhibition assay (MGIA) for the early evaluation of TB vaccine candidates and assessment of protective immunity: a protocol for non-human primate cells

“…BCG-induced protection against pulmonary TB is lowest in regions close to the equator such as sub-Saharan Africa and India where an effective vaccine is most desperately needed 3 . However, development of a successful TB vaccine is severely hampered by the lack of a validated correlate or biomarker of protection 4 . It remains unclear which aspects of the immune response confer protection from TB disease, and therefore which parameters to target with a vaccine and to assess as a reliable measure of protective efficacy.…”

Accelerating tuberculosis vaccine trials with diagnostic and prognostic biomarkers

“…In particular, we focus on biomarkers in the context of preclinical design and clinical development of vaccines against TB. Some aspects addressed in this review have partially also been covered in some recent reviews focusing more particular on TB diagnosis [21], risk [22], and vaccine development [23]. Center of figure depicts major steps from initial infection, to latency and active disease.…”