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arXiv · 1509.06778

On the impact of Masking and Blocking Hypotheses for measuring efficacy of new tuberculosis vaccines

Sergio Arregui·Joaquín Sanz·Dessislava Marinova·Carlos Martín·Yamir Moreno
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Abstract

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, showing a wide range of protection in adults against pulmonary TB. Previous studies indicate that this failure is related to 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: the masking, (previous sensitization confers some level of protection against TB), and the blocking (previous immune response prevent vaccine taking of a new TB vaccine), effects. In this work we introduce a series of models to discriminate between masking and blocking mechanisms and address their relative likelihood. The application of our models to interpret the results coming from the BCG-REVAC clinical trials, specifically designed for the study of sources of efficacy variability yields estimates that are consistent with high levels of blocking (41% in Manaus -95% C.I. [14%-68%]- and 96% in Salvador -95% C.I. [52%-100%]-), and no support for masking to play any relevant role in modifying vaccine efficacy either alone or aside 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 if applied on individuals previously exposed to mycobacterial antigens.

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Sergio Arregui, Joaquín Sanz, Dessislava Marinova, Carlos Martín, Yamir Moreno. 2015-09-22. On the impact of Masking and Blocking Hypotheses for measuring efficacy of new tuberculosis vaccines. https://arxiv.org/abs/1509.06778

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