48654 20230111103815.0 doi 10.7717/peerj.1513 sideral 94583 ART-2016-94583 eng Arregui, S. Universidad de Zaragoza (orcid)0000-0003-3259-0933 On the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines 2016 Access copy available to the general public Unrestricted Over the past 60 years, the Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used worldwide to prevent tuberculosis (TB). However, BCG has shown a very variable efficacy in different trials, offering a wide range of protection in adults against pulmonary TB. One of the most accepted hypotheses to explain these inconsistencies points to the existence of a pre-existing immune response to antigens that are common to environmental sources of mycobacterial antigens and Mycobacterium tuberculosis. Specifically, two different mechanisms have been hypothesized to explain this phenomenon: The masking and the blocking effects. According to masking hypothesis, previous sensitization confers some level of protection against TB that masks vaccine''s effects. In turn, the blocking hypothesis postulates that previous immune response prevents vaccine taking of a new TB vaccine. In this work we introduce a series of models to discriminate between masking and blocking mechanisms and address their relative likelihood. We apply our methodology to the data reported by BCG-REVAC clinical trials, which were specifically designed for studying BCG efficacy variability. Our results yield estimates that are consistent with high levels of blocking (41% in Manaus-95% CI 14-68]-and 96% in Salvador-95% CI 52-100]-). Moreover, we also show that masking does not play any relevant role in modifying vaccine''s efficacy either alone or in addition to blocking. The quantification of these effects around a plausible model constitutes a relevant step towards impact evaluation of novel anti-tuberculosis vaccines, which are susceptible of being affected by similar effects, especially if applied on individuals previously exposed to mycobacterial antigens. info:eu-repo/grantAgreement/EC/FP7/241745/EU/Discovery and preclinical development of new generation tuberculosis vaccines/NEWTBVAC info:eu-repo/grantAgreement/EC/FP7/317532/EU/Foundational Research on MULTIlevel comPLEX networks and systems/MULTIPLEX info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020 This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 643381-TBVAC2020 info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P info:eu-repo/grantAgreement/ES/MINECO/FIS2011-25167 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 2.177 2016 MULTIDISCIPLINARY SCIENCES 19 / 63 = 0.302 2016 Q2 T1 1.124 2016 Agricultural and Biological Sciences (miscellaneous) 2016 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2016 Q1 Medicine (miscellaneous) 2016 Q1 Neuroscience (miscellaneous) 2016 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sanz, J. (orcid)0000-0002-2980-9685 Marinova, D. Universidad de Zaragoza (orcid)0000-0001-8644-120X Martín, C. Universidad de Zaragoza (orcid)0000-0003-2993-5478 Moreno, Y. 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 2016, 2 (2016), [21 pp.] PeerJ PeerJ 2167-8359 6612402 http://zaguan.unizar.es/record/48654/files/texto_completo.pdf Versión publicada 98583 http://zaguan.unizar.es/record/48654/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:48654 articulos driver 2023-01-11-10:03:58 ARTICLE