On the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines

Arregui, S. (Universidad de Zaragoza) ; Sanz, J. ; Marinova, D. (Universidad de Zaragoza) ; Martín, C. (Universidad de Zaragoza) ; Moreno, Y. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.7717/peerj.1513

Año: 2016

Publicado en: PeerJ 2016, 2 (2016), [21 pp.]
ISSN: 2167-8359

Factor impacto JCR: 2.177 (2016)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 19 / 63 = 0.302 (2016) - Q2 - T1

Factor impacto SCIMAGO: 1.124 - Agricultural and Biological Sciences (miscellaneous) (Q1) - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Medicine (miscellaneous) (Q1) - Neuroscience (miscellaneous) (Q2)

Financiación: info:eu-repo/grantAgreement/EC/FP7/241745/EU/Discovery and preclinical development of new generation tuberculosis vaccines/NEWTBVAC
Financiación: info:eu-repo/grantAgreement/EC/FP7/317532/EU/Foundational Research on MULTIlevel comPLEX networks and systems/MULTIPLEX
Financiación: 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
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/FIS2011-25167

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)