87611 20230111103825.0 doi 10.1038/s41467-019-13387-9 sideral 115822 ART-2019-115822 eng Tovar, Mario Universidad de Zaragoza Bridging the gap between efficacy trials and model-based impact evaluation for new tuberculosis vaccines 2019 Access copy available to the general public Unrestricted In Tuberculosis (TB), given the complexity of its transmission dynamics, observations of reduced epidemiological risk associated with preventive interventions can be difficult to translate into mechanistic interpretations. Specifically, in clinical trials of vaccine efficacy, a readout of protection against TB disease can be mapped to multiple dynamical mechanisms, an issue that has been overlooked so far. Here, we describe this limitation and its effect on model-based evaluations of vaccine impact. Furthermore, we propose a methodology to analyze efficacy trials that circumvents it, leveraging a combination of compartmental models and stochastic simulations. Using our approach, we can disentangle the different possible mechanisms of action underlying vaccine protection effects against TB, conditioned to trial design, size, and duration. Our results unlock a deeper interpretation of the data emanating from efficacy trials of TB vaccines, which renders them more interpretable in terms of transmission models and translates into explicit recommendations for vaccine developers. info:eu-repo/grantAgreement/ES/DGA/E36-17R info:eu-repo/grantAgreement/ES/MICINN/RYC-2017-23560 info:eu-repo/grantAgreement/ES/MINECO/FIS2017-87519-P info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 12.121 2019 MULTIDISCIPLINARY SCIENCES 6 / 71 = 0.085 2019 Q1 T1 5.569 2019 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2019 Q1 Physics and Astronomy (miscellaneous) 2019 Q1 Chemistry (miscellaneous) 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Arregui, Sergio (orcid)0000-0003-3259-0933 Marinova, Dessislava Universidad de Zaragoza (orcid)0000-0001-8644-120X Martín, Carlos Universidad de Zaragoza (orcid)0000-0003-2993-5478 Sanz, Joaquín Universidad de Zaragoza (orcid)0000-0002-2980-9685 Moreno, Yamir Universidad de Zaragoza (orcid)0000-0002-0895-1893 1008 630 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Microbiología 1008 X Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Proy. investigación HQA 2004 405 Universidad de Zaragoza Dpto. Física Teórica Área Física Teórica 10 (2019), 5457 1-10 NATURE COMMUNICATIONS NATURE COMMUNICATIONS 2041-1723 781462 http://zaguan.unizar.es/record/87611/files/texto_completo.pdf Versión publicada 63811 http://zaguan.unizar.es/record/87611/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:87611 articulos driver 2023-01-11-10:07:23 ARTICLE