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

Ana Balseiro,Mariano Domingo,Joseba M Garrido,Bernat Pérez De Val,Enric Vidal,Iker A Sevilla,Ramón A Juste,Miguel Prieto,Xavier Moll,Yvonne Espada,Raúl Altuzarra

doi:10.1371/journal.pone.0180546

Abstract

Background/AimsAnimal 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.MethodsEighteen 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.ResultsAll 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.ConclusionsThis 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.

Highlights

Animal tuberculosis (TB) is a mycobacterial disease that affects a broad range of mammals including domestic animals, wildlife and humans
This study proposes a reliable new experimental model for a better understanding of tuberculosis in sheep
bacille Calmette-Guerin (BCG) vaccination offers an effective prospect for controlling the disease

Summary

Introduction

Animal tuberculosis (TB) is a mycobacterial disease that affects a broad range of mammals including domestic animals, wildlife and humans. It is caused by members of the Mycobacterium tuberculosis complex (MTBC), most commonly Mycobacterium bovis and Mycobacterium caprae [1]. It is one of the most complex animal health problems that the ungulate farming industry faces today [2]. In Europe animal TB involves a multi-host system where domestic (cattle and goats) and wildlife (badger, wild boar and red deer) have a relevant role that varies between regions, depending on climate, habitat and husbandry factors [4]. Given the abundance and widespread distribution of domestic sheep in Europe and elsewhere, that role may have important implications for global animal TB control, since sheep are not routinely subjected to the periodic diagnostic testing within the National Programmes to eradicate bovine TB in many countries where TB is prevalent in cattle or goats [5]

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