TY - JOUR
T1 - Genetic screening for the protective antigenic targets of BCG vaccination
AU - Smith, Alex A.
AU - Villarreal-Ramos, Bernardo
AU - Mendum, Tom A.
AU - Williams, Kerstin J.
AU - Jones, Gareth J.
AU - Wu, Huihai
AU - McFadden, Johnjoe
AU - Vordermeier, H. Martin
AU - Stewart, Graham R.
N1 - Funding Information:
This study was supported by the UK BBSRC (grant number BB/L024209/1) and an APHA/University of Surrey PhD studentship. We used biobanked PBMC generated in experiments funded by the Department of Environment, Food and Rural Affairs (DEFRA) UK and the Welsh and Scottish Governments.The authors would like to thank Michael Coad and Sabine Steinbach for their assistance with the immunoassays. We also acknowledge the excellent support provided by the animal team at the APHA.
Funding Information:
This study was supported by the UK BBSRC (grant number BB/L024209/1 ) and an APHA/University of Surrey PhD studentship. We used biobanked PBMC generated in experiments funded by the Department of Environment, Food and Rural Affairs (DEFRA) UK and the Welsh and Scottish Governments .
Publisher Copyright:
© 2020
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - Antigens
KW - BCG
KW - Bovine tuberculosis TB
KW - Cattle vaccine
KW - Transposon mutagenesis
KW - Immunogenicity, Vaccine
KW - Cytokines/immunology
KW - Tuberculosis, Bovine/immunology
KW - DNA Transposable Elements
KW - Vaccination/veterinary
KW - Mycobacterium tuberculosis/genetics
KW - Animals
KW - BCG Vaccine/administration & dosage
KW - Cattle
KW - Antigens, Bacterial/administration & dosage
KW - Leukocytes, Mononuclear/immunology
KW - Mutation
UR - http://www.scopus.com/inward/record.url?scp=85089438876&partnerID=8YFLogxK
U2 - 10.1016/j.tube.2020.101979
DO - 10.1016/j.tube.2020.101979
M3 - Article
C2 - 32814303
AN - SCOPUS:85089438876
SN - 1472-9792
VL - 124
JO - Tuberculosis
JF - Tuberculosis
M1 - 101979
ER -
