TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development

Abstract

TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal.

The BCGΔBCG1419c Vaccine Candidate Reduces Lung Pathology, IL-6, TNF-α, and IL-10 During Chronic TB Infection

“…This finding along with the lack of success of the most advanced vaccine candidates in clinical trials to improve protection versus TB make a strong argument to look for other potential vaccine candidates exploring alternate hypotheses. Moreover, the potential of following strategies that encompass from discovery to clinical trials has proven promising results ( Kaufmann et al, 2017b ). While the role of biofilms in TB remains a matter of ongoing research, this work further demonstrates that BCGΔBCG1419c protects against chronic infection by M. tuberculosis in diverse mouse models, calling for additional assays as already suggested here, including assays in models than more closely resemble LTBI.…”

Proteomics of Mycobacterium Infection: Moving towards a Better Understanding of Pathogen-Driven Immunomodulation

“…Furthermore, we also only begin to understand the impact of the different virulence factor secreted upon Mtb infection, which additionally interfere with host pathways to promote Mtb survival and growth ( 12 ). Together with the fact that the existing BCG vaccine is inefficient and needs further improvement and alternatives ( 13 ), it is clear that we need more knowledge of mycobacterial pathogenesis and the host factors manipulated by Mtb allowing to establish its intracellular niche. In particular, a better understanding of host immune responses and the involved mechanisms controlling the infection are needed, because they affect disease outcome as well as TB pathology.…”

Vaccination Against Tuberculosis: Revamping BCG by Molecular Genetics Guided by Immunology

“…BCG fails to protect against pulmonary TB, which is not only the most prevalent form of disease but also the major source of transmission. This has led to several attempts to design novel vaccination regimens (18…”

“…In 2018, 10 million individuals fell ill with this disease and 1.5 million died (11) (Figure 1). The early 21st century has witnessed increasing R&D efforts for novel TB vaccines (12)(13)(14)(15)(16)(17)(18)(19). These include subunit-adjuvant formulations comprising fusion proteins of Mtb, viral vectored vaccines expressing one or more antigens of Mtb, killed mycobacterial vaccines and viable attenuated mycobacterial vaccines.…”