000048654 001__ 48654
000048654 005__ 20230111103815.0
000048654 0247_ $$2doi$$a10.7717/peerj.1513
000048654 0248_ $$2sideral$$a94583
000048654 037__ $$aART-2016-94583
000048654 041__ $$aeng
000048654 100__ $$0(orcid)0000-0003-3259-0933$$aArregui, S.$$uUniversidad de Zaragoza
000048654 245__ $$aOn the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines
000048654 260__ $$c2016
000048654 5060_ $$aAccess copy available to the general public$$fUnrestricted
000048654 5203_ $$aOver 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.
000048654 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/FIS2011-25167$$9info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 643381-TBVAC2020$$9info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020$$9info:eu-repo/grantAgreement/EC/FP7/317532/EU/Foundational Research on MULTIlevel comPLEX networks and systems/MULTIPLEX$$9info:eu-repo/grantAgreement/EC/FP7/241745/EU/Discovery and preclinical development of new generation tuberculosis vaccines/NEWTBVAC
000048654 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000048654 590__ $$a2.177$$b2016
000048654 591__ $$aMULTIDISCIPLINARY SCIENCES$$b19 / 63 = 0.302$$c2016$$dQ2$$eT1
000048654 592__ $$a1.124$$b2016
000048654 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2016$$dQ1
000048654 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2016$$dQ1
000048654 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000048654 593__ $$aNeuroscience (miscellaneous)$$c2016$$dQ2
000048654 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000048654 700__ $$0(orcid)0000-0002-2980-9685$$aSanz, J.
000048654 700__ $$0(orcid)0000-0001-8644-120X$$aMarinova, D.$$uUniversidad de Zaragoza
000048654 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000048654 700__ $$0(orcid)0000-0002-0895-1893$$aMoreno, Y.$$uUniversidad de Zaragoza
000048654 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología
000048654 7102_ $$11008$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cProy. investigación HQA
000048654 7102_ $$12004$$2405$$aUniversidad de Zaragoza$$bDpto. Física Teórica$$cÁrea Física Teórica
000048654 773__ $$g2016, 2 (2016), [21 pp.]$$pPeerJ$$tPeerJ$$x2167-8359
000048654 8564_ $$s6612402$$uhttps://zaguan.unizar.es/record/48654/files/texto_completo.pdf$$yVersión publicada
000048654 8564_ $$s98583$$uhttps://zaguan.unizar.es/record/48654/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000048654 909CO $$ooai:zaguan.unizar.es:48654$$particulos$$pdriver
000048654 951__ $$a2023-01-11-10:03:58
000048654 980__ $$aARTICLE