127820 20241125101158.0 doi 10.1038/s41467-023-40976-6 sideral 134940 ART-2023-134940 eng Tovar, M. Universidad de Zaragoza Addressing mechanism bias in model-based impact forecasts of new tuberculosis vaccines 2023 Access copy available to the general public Unrestricted In tuberculosis (TB) vaccine development, multiple factors hinder the design and interpretation of the clinical trials used to estimate vaccine efficacy. The complex transmission chain of TB includes multiple routes to disease, making it hard to link the vaccine efficacy observed in a trial to specific protective mechanisms. Here, we present a Bayesian framework to evaluate the compatibility of different vaccine descriptions with clinical trial outcomes, unlocking impact forecasting from vaccines whose specific mechanisms of action are unknown. Applying our method to the analysis of the M72/AS01E vaccine trial -conducted on IGRA+ individuals- as a case study, we found that most plausible models for this vaccine needed to include protection against, at least, two over the three possible routes to active TB classically considered in the literature: namely, primary TB, latent TB reactivation and TB upon re-infection. Gathering new data regarding the impact of TB vaccines in various epidemiological settings would be instrumental to improve our model estimates of the underlying mechanisms. info:eu-repo/grantAgreement/ES/DGA/B49-23R-NeuroBioSys info:eu-repo/grantAgreement/ES/DGA/E36-23R-FENOL info:eu-repo/grantAgreement/ES/DGA-IIU/796-2019 info:eu-repo/grantAgreement/ES/MICINN/PID2019-106859GA-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2020-115800GB-I00 info:eu-repo/grantAgreement/ES/MICINN/RYC-2017-23560 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 14.7 2023 MULTIDISCIPLINARY SCIENCES 8 / 134 = 0.06 2023 Q1 T1 4.887 2023 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2023 Q1 Physics and Astronomy (miscellaneous) 2023 Q1 Chemistry (miscellaneous) 2023 Q1 24.9 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Moreno, Y. Universidad de Zaragoza (orcid)0000-0002-0895-1893 Sanz, J. Universidad de Zaragoza (orcid)0000-0002-2980-9685 2004 405 Universidad de Zaragoza Dpto. Física Teórica Área Física Teórica 14, 5312 (2023), 12 Nature communications 2041-1723 2774407 http://zaguan.unizar.es/record/127820/files/texto_completo.pdf Versión publicada 2670584 http://zaguan.unizar.es/record/127820/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:127820 articulos driver 2024-11-22-12:10:15 ARTICLE