Development of a BCG challenge model for the testing of vaccine candidates against tuberculosis in cattle

Bernardo Villarreal-Ramos,Stefan Berg,Laura Chamberlain,Helen Mcshane,R Glyn Hewinson,Derek Clifford,Martin Vordermeier

doi:10.1016/j.vaccine.2014.08.009

Bernardo Villarreal-Ramos, Stefan Berg + Show 5 more

Open Access

https://doi.org/10.1016/j.vaccine.2014.08.009

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Abstract

Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria.

Highlights

Mycobacterium bovis belongs to the Mycobacterium tuberculosis complex of bacteria and is the main aetiologic agent of bovine tuberculosis (BTB) as well as being responsible for a proportion of cases of human tuberculosis (TB)
BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates
In this work we have evaluated an intranodal bacillus Calmette-Guerin (BCG) challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses

Summary

Introduction

Mycobacterium bovis belongs to the Mycobacterium tuberculosis complex of bacteria and is the main aetiologic agent of bovine tuberculosis (BTB) as well as being responsible for a proportion of cases of human tuberculosis (TB). It is possible to carry out vaccination and challenge experiments in cattle to determine whether a given vaccine or vaccination regimen confers protection against BTB. These experiments require the use of large animal biosafety level 3 (BSL3) facilities which are expensive to maintain and are often oversubscribed. Cheaper and faster gating criteria should be available to support the decision making process of whether a vaccine should be tested in cattle for protective efficacy in such vaccination and challenge experiments.

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