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Genetic screening for the protective antigenic targets of BCG vaccination

Smith, Alex A., Villarreal-Ramos, Bernardo, Mendum, Thomas A., Williams, Kerstin J., Jones, Gareth J., Wu, Huihai, McFadden, Johnjoe, Vordermeier, H. Martin and Stewart, Graham R. (2020) Genetic screening for the protective antigenic targets of BCG vaccination TUBERCULOSIS, 124, 101979.

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Abstract

Bovine tuberculosis is an important animal health problem and the predominant cause of zoonotic tuberculosis worldwide. It results in serious economic burden due to losses in productivity and the cost of control programmes. Control could be greatly improved by the introduction of an efficacious cattle vaccine but the most likely candidate, BCG, has several limitations including variable efficacy. Augmentation of BCG with a subunit vaccine booster has been shown to increase protection but the selection of antigens has hitherto been left largely to serendipity. In the present study, we take a rational approach to identify the protective antigens of BCG, selecting a BCG transposon mutant library in naïve and BCG-vaccinated cattle. Ten mutants had increased relative survival in vaccinated compared to naïve cattle, consistent with loss of protective antigen targets making the mutants less visible to the BCG immune response. The immunogenicity of three putative protective antigens, BCG_0116, BCG_0205 (YrbE1B) and BCG_1448 (PPE20) was investigated using peptide pools and PBMCs from BCG vaccinated cattle. BCG vaccination induced PBMC to release elevated levels of IP10, IL-17a and IL-10 in response to all three antigens. Taken together, the data supports the further study of these antigens for use in subunit vaccines.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences
Authors :
NameEmailORCID
Smith, Alex A.alex.smith@surrey.ac.uk
Villarreal-Ramos, Bernardo
Mendum, Thomas A.T.Mendum@surrey.ac.uk
Williams, Kerstin J.k.j.williams@surrey.ac.uk
Jones, Gareth J.
Wu, HuihaiH.Wu@surrey.ac.uk
McFadden, JohnjoeJ.Mcfadden@surrey.ac.uk
Vordermeier, H. Martin
Stewart, Graham R.G.Stewart@surrey.ac.uk
Date : September 2020
Funders : BBSRC (Biotechnology and Biological Science Research Council)
DOI : 10.1016/j.tube.2020.101979
Copyright Disclaimer : © 2020 Published by Elsevier Ltd.
Uncontrolled Keywords : Bovine tuberculosis TB; BCG; Antigens; Cattle vaccine; Transposon mutagenesis
Depositing User : Diane Maxfield
Date Deposited : 05 Oct 2020 16:16
Last Modified : 05 Oct 2020 16:16
URI: http://epubs.surrey.ac.uk/id/eprint/858662

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