TY - JOUR
T1 - End-point definition and trial design to advance tuberculosis vaccine development
AU - Garcia-Basteiro, Alberto L.
AU - White, Richard G.
AU - Tait, Dereck
AU - Schmidt, Alexander C.
AU - Rangaka, Molebogeng X.
AU - Quaife, Matthew
AU - Nemes, Elisa
AU - Mogg, Robin
AU - Hill, Philip C.
AU - Harris, Rebecca C.
AU - Hanekom, Willem A.
AU - Frick, Mike
AU - Fiore-Gartland, Andrew
AU - Evans, Tom
AU - Dagnew, Alemnew F.
AU - Churchyard, Gavin
AU - Cobelens, Frank
AU - Behr, Marcel A.
AU - Hatherill, Mark
N1 - Funding Information: Conflict of interest: D. Tait is a salaried employee IAVI NPC. E. Nemes has received grants or contracts from US National Institutes of Health, Bill and Melinda Gates Foundation and Gates Medical Research Institute, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: “TB immune correlates” Leadership Team. R. Mogg advises that support for the present manuscript has been received from Bill and Melinda Gates, for which they are currently an employee. Consulting fees received from PMV Pharma, Autobahn Therapeutics, Asher Biotherapeutics, Inc., and Bill and Melinda Gates Foundation, outside the submitted work. Unpaid participation on a Data Safety Monitoring Board or Advisory Board for COnV-ert DSMB, outside the submitted work. Stock or stock options held for Takeda, outside the submitted work. R.C. Harris is current employee of Sanofi Pasteur. Shares held for Sanofi Pasteur, outside the submitted work. A. Fiore-Gartland reports support for the present manuscript received from Bill and Melinda Gates Foundation, grant-based funding for Vaccines and Immunology Statistical Center. T. Evans has received consulting fees from Vir Biotechnology, outside the submitted work. Participation on an advisory board to GHIF on a recombinant BCG project run by Serum Institute of India, outside the submitted work. A.F Dagnew is a current employee of the Bill and Melinda Gates Medical Research Institute. F. Cobelens has received grants or contracts from EDCTP and the Bill and Melinda Gates Foundation, outside the submitted work. Support for attending meetings and/or travel received from Tuberculosis Vaccine Initiative, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for Tuberculosis Vaccine Initiative and EDCTP Tuberculosis Vaccine Oversight Committee, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Coalition for TB Vaccine Discovery, Bill and Melinda Gates Foundation. M.A. Behr has received grants or contracts from Canadian Institutes for Health Research (Foundation Grant) and Canada Research Chair, outside the submitted work. Patents planned, issued or pending: Molecular differences between species of the M. tuberculosis complex Grant US-7364740-B2. Priority date 1998/08/25. Participated on the Endpoint Committee of RCT comparing 9 INH to 4 Rif (Menzies, NEJM, 2018). M. Hatherill reports institutional clinical trial grants to University of Cape Town, outside the submitted work. The remaining authors have nothing to disclose. Funding Information: Support statement: R.G. White is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 & INV-001754), and the WHO (2020/985800-0). Publisher Copyright: © The authors 2022.
PY - 2022/6/30
Y1 - 2022/6/30
N2 - Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgently needed. There are several new vaccine candidates at different stages of clinical development. Given the limited funding for vaccine development, it is crucial that trial designs are as efficient as possible. Prevention of infection (POI) approaches offer an attractive opportunity to accelerate new candidate vaccines to advance into large and expensive prevention of disease (POD) efficacy trials. However, POI approaches are limited by imperfect current tools to measure Mycobacterium tuberculosis infection end-points. POD trials need to carefully consider the type and number of microbiological tests that define TB disease and, if efficacy against subclinical (asymptomatic) TB disease is to be tested, POD trials need to explore how best to define and measure this form of TB. Prevention of recurrence trials are an alternative approach to generate proof of concept for efficacy, but optimal timing of vaccination relative to treatment must still be explored. Novel and efficient approaches to efficacy trial design, in addition to an increasing number of candidates entering phase 2-3 trials, would accelerate the long-standing quest for a new TB vaccine.
AB - Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgently needed. There are several new vaccine candidates at different stages of clinical development. Given the limited funding for vaccine development, it is crucial that trial designs are as efficient as possible. Prevention of infection (POI) approaches offer an attractive opportunity to accelerate new candidate vaccines to advance into large and expensive prevention of disease (POD) efficacy trials. However, POI approaches are limited by imperfect current tools to measure Mycobacterium tuberculosis infection end-points. POD trials need to carefully consider the type and number of microbiological tests that define TB disease and, if efficacy against subclinical (asymptomatic) TB disease is to be tested, POD trials need to explore how best to define and measure this form of TB. Prevention of recurrence trials are an alternative approach to generate proof of concept for efficacy, but optimal timing of vaccination relative to treatment must still be explored. Novel and efficient approaches to efficacy trial design, in addition to an increasing number of candidates entering phase 2-3 trials, would accelerate the long-standing quest for a new TB vaccine.
UR - http://www.scopus.com/inward/record.url?scp=85131639937&partnerID=8YFLogxK
U2 - https://doi.org/10.1183/16000617.0044-2022
DO - https://doi.org/10.1183/16000617.0044-2022
M3 - Article
C2 - 35675923
SN - 0905-9180
VL - 31
JO - European Respiratory Review
JF - European Respiratory Review
IS - 164
M1 - 220044
ER -