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

PLoS One. 2019 Apr 19;14(4):e0214859. doi: 10.1371/journal.pone.0214859. eCollection 2019.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / immunology*
  • Bacterial Load
  • Disease Reservoirs / microbiology
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Microbial Viability / immunology
  • Models, Biological
  • Mustelidae / immunology*
  • Mustelidae / microbiology*
  • Mycobacterium bovis / immunology*
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control
  • Tuberculosis / veterinary
  • Upper Gastrointestinal Tract / immunology
  • Upper Gastrointestinal Tract / metabolism
  • Upper Gastrointestinal Tract / microbiology
  • Vaccination / methods
  • Vaccination / veterinary*

Substances

  • BCG Vaccine

Associated data

  • figshare/10.6084/m9.figshare.7925288.v1
  • figshare/10.6084/m9.figshare.7925333.v1

Grants and funding

GAW, PW, SG, SL and MAC were supported by grant SE3246 awarded by the UK government Department for Environment, Food and Rural Affairs (Defra) - https://www.gov.uk/government/organisations/department-for-environment-food-rural-affairs. Defra did not play a role in the study design, data collection and analysis, or preparation of the manuscript. Defra did give permission to publish.