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Survival of Mycobacterium bovis BCG oral vaccine during transit through a dynamic in vitro model simulating the upper gastrointestinal tract of badgers

Manganelli, Riccardo, Williams, Gareth A., Koenen, Marjorie E., Havenaar, Robert, Wheeler, Paul, Gowtage, Sonya, Lesellier, Sandrine and Chambers, Mark A. (2019) Survival of Mycobacterium bovis BCG oral vaccine during transit through a dynamic in vitro model simulating the upper gastrointestinal tract of badgers PLoS ONE, 14 (4), e0214859.

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Abstract

In developing an oral bait BCG vaccine against tuberculosis in badgers we wanted to understand the conditions of the gastrointestinal tract and their impact on vaccine viability. Conditions mimicking stomach and small-intestine caused substantial reduction in BCG viability. We performed in vivo experiments using a telemetric pH monitoring system and used the data to parameterise a dynamic in vitro system (TIM-1) of the stomach and small intestine. Some BCG died in the stomach compartment and through the duodenum and jejunum compartments. BCG survival in the stomach was greatest when bait was absent but by the time BCG reached the jejunum, BCG viability was not significantly affected by the presence of bait. Our data suggest that from a starting quantity of 2.85 ± 0.45 x 108 colony-forming units of BCG around 2 log10 may be killed before delivery to the intestinal lymphoid tissue. There are economic arguments for reducing the dose of BCG to vaccinate badgers orally. Our findings imply this could be achieved if we can protect BCG from the harsh environment of the stomach and duodenum. TIM-1 is a valuable, non-animal model with which to evaluate and optimise formulations to maximise BCG survival in the gastrointestinal tract.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
NameEmailORCID
Manganelli, Riccardo
Williams, Gareth A.
Koenen, Marjorie E.
Havenaar, Robert
Wheeler, Paul
Gowtage, Sonya
Lesellier, Sandrine
Chambers, Mark A.m.chambers@surrey.ac.uk
Date : 19 April 2019
Funders : Department for Environment, Food and Rural Affairs (Defra)
DOI : 10.1371/journal.pone.0214859
Copyright Disclaimer : © 2019 Williams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Diane Maxfield
Date Deposited : 03 Sep 2019 13:44
Last Modified : 03 Sep 2019 13:44
URI: http://epubs.surrey.ac.uk/id/eprint/852532

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