2026-06-14T05:06:23Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/57632025-05-27T12:28:30Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Arregui, Sergio
author
Sanz, Joaquín
author
Marinova, Dessislava
author
Martín, Carlos
author
Moreno, Yamir
funder
Unión Europea. Comisión Europea
funder
Gobierno de Aragón (España)
funder
Foundation CHU Sainte-Justine
funder
Government of Quebec (Canadá)
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
2018-03-20T10:50:56Z
2018-03-20T10:50:56Z
2016-02-11
PeerJ. 2016 Feb 11;4:e1513.
10.7717/peerj.1513
2167-8359
PeerJ
26893956
http://hdl.handle.net/20.500.12105/5763
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.
eng
BCG
Blocking
Clinical trials
Environmental sensitization
Masking
TB vaccines
Tuberculosis
On the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines
research article
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