Assessment of BCG and inactivated Mycobacterium bovis vaccines in an experimental tuberculosis infection model in sheep

PLoS One. 2017 Jul 5;12(7):e0180546. doi: 10.1371/journal.pone.0180546. eCollection 2017.

Abstract

Background/aims: Animal tuberculosis (TB) is a complex animal health problem that causes disruption to trade and significant economic losses. TB involves a multi-host system where sheep, traditionally considered a rare host of this infection, have been recently included. The aims of this study were to develop an experimental TB infection model in sheep with a Mycobacterium caprae field strain isolated from a tuberculous diseased ewe, and to use this to evaluate the safety and efficacy of two vaccines against TB in sheep, the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine.

Methods: Eighteen 2 month-old lambs were experimentally challenged with M. caprae by the endotracheal route (1.5 × 103 CFU). They were separated per treatment group into parenterally vaccinated with a live BCG Danish strain vaccine (n = 6), orally vaccinated with a suspension of HIMB (n = 6) and unvaccinated controls (n = 6). Clinical, immunological, pathological and bacteriological parameters of infection were measured.

Results: All lambs were successfully infected and developed gross TB lesions in the respiratory system. The BCG vaccine conferred considerable protection against experimental TB in lambs, as measured by a reduction of the gross lesion volumes and bacterial load. However, HIMB vaccinated animals did not show protection.

Conclusions: This study proposes a reliable new experimental model for a better understanding of tuberculosis in sheep. BCG vaccination offers an effective prospect for controlling the disease. Moreover alternative doses and/or routes of administration should be considered to evaluate the efficacy of the HIMB vaccine candidate.

MeSH terms

  • Animals
  • BCG Vaccine*
  • Mycobacterium bovis* / immunology
  • Sheep
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control*
  • Tuberculosis / veterinary*
  • Vaccination
  • Vaccines, Inactivated

Substances

  • BCG Vaccine
  • Vaccines, Inactivated

Grants and funding

This work was funded by a grant from Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), reference number RTA2014-0002-C02-01 (FEDER co-funded). IRTA is supported by CERCA Programme / Generalitat de Catalunya.