Bridging the gap between efficacy trials and model-based impact evaluation for new tuberculosis vaccines

Tovar, Mario (Universidad de Zaragoza) ; Arregui, Sergio ; Marinova, Dessislava (Universidad de Zaragoza) ; Martín, Carlos (Universidad de Zaragoza) ; Sanz, Joaquín (Universidad de Zaragoza) ; Moreno, Yamir (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41467-019-13387-9

Año: 2019

Publicado en: NATURE COMMUNICATIONS 10 (2019), 5457 1-10
ISSN: 2041-1723

Factor impacto JCR: 12.121 (2019)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 6 / 71 = 0.085 (2019) - Q1 - T1

Factor impacto SCIMAGO: 5.569 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/E36-17R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC-2017-23560
Financiación: info:eu-repo/grantAgreement/ES/MINECO/FIS2017-87519-P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Área Física Teórica (Dpto. Física Teórica)