Accelerating tuberculosis vaccine trials with diagnostic and prognostic biomarkers

Abstract

The most recent estimates on tuberculosis (TB) morbidity and mortality reveal that the global disease burden is even higher than previously assumed. Better drugs, diagnostics and vaccines are major requirements to control the ongoing TB pandemic. The high complexity of the infectious process and the underlying pathology, however, challenge elucidation of protective immune mechanisms at the various stages towards active TB disease, which need to be understood for rational design of novel intervention measures. Areas covered: Next to the more classical approaches, host biomarkers increasingly receive attention as promising tools on our way to control the disease. In the area of diagnosis, host biomarkers are recognized as promising new means because the identification of small biosignatures with high discriminatory and even prognostic potential has stimulated the hope that rapid and easy-to-perform diagnosis and prognosis will become possible in the near future. For rational design of new vaccine candidates, correlates of protection are highly desirable. High-throughput systems-vaccinology will boost the identification of such biomarker profiles. Expert commentary: Considering their potential to accelerate development of better diagnostics and vaccines, host biomarkers should be firmly integrated into future TB research.

Peptide microarray-based identification of dormancy-associated Mycobacterium tuberculosis antigens inducing immune responses among latent tuberculosis infection individuals in Thailand

“…Specifically, LTBI individuals have a substantial risk (5–10% in their lifetime) of developing active tuberculosis (ATB), and thereby maintaining the incidence of new TB cases 2 . To tackle this problem, an idea based on prevention of TB reactivation among those with LTBI has been raised as a potential approach 3 . Until now, the World Health Organization (WHO) has recommended a vaccination strategy which enhances immune responses that suppress TB reactivation 4 .…”

Progress and challenges in TB vaccine development

“…Success in studies of individuals with LTBI and active TB patients has led to host biomarkers becoming an integral part of future TB control. Proof of principle has been given that biomarkers can distinguish between active TB disease and LTBI, and evidence is accumulating that biomarkers can predict progression to active TB 31 . Thus, it has been demonstrated that small-sized biosignatures comprising 3-4 transcripts are capable of reliably discriminating TB disease from LTBI and medium-sized biosignatures comprising 16 transcripts or less allow prediction of active TB by diagnosing incipient, subclinical TB 21 .…”

TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development

“…We will not use more exploratory assays in this WP, as they are less standardized, but PBMC and serum will be stored from all subjects at all time-points using harmonized SOP, so that further immunological evaluation can be performed as the field of BMs develops. In this regard, this WP will work closely with WP5 to monitor progress in the field of BM development ( 4 , 5 , 40 , 41 ). Furthermore, ongoing work, for example, within the infrastructural FP7 EURIPRED project, to standardize the PBMC mycobacterial growth inhibition assay (MGIA), will be monitored and this assay will be conducted on cryopreserved material if the assay is deemed sufficiently fit for this purpose ( 68 ).…”