Type

Journal Article

Authors

Peter Andersen
Else Marie Agger
Carina Vingsbo Lundberg
Gary K Schoolnik
Gregory Dolganov
Joseph P Cassidy
Jes Dietrich
Claus Aagaard
Truc Hoang

Subjects

Microbiology

Topics
gene expression genome organization vaccination tuberculosis vaccines immune system cd4 t cells mycobacterium tuberculosis exposure

ESAT-6 (EsxA) and TB10.4 (EsxH) Based Vaccines for Pre- and Post-Exposure Tuberculosis Vaccination. (2013)

Abstract The ESX systems from Mycobacterium tuberculosis are responsible for the secretion of highly immunogenic proteins of key importance for bacterial survival and growth. The two prototypic proteins, ESAT-6 (EsxA from ESX-1) and TB10.4 (EsxH from ESX-3) share a lot of characteristics regarding genome organization, size, antigenic properties, and vaccine potential but the two molecules clearly have very different roles in bacterial physiology. To further investigate the role of ESAT-6 and TB10.4 as preventive and post-exposure tuberculosis vaccines, we evaluated four different fusion-protein vaccines; H1, H4, H56 and H28, that differ only in these two components. We found that all of these vaccines give rise to protection in a conventional prophylactic vaccination model. In contrast, only the ESAT-6-containing vaccines resulted in significant protection against reactivation, when administered post-exposure. This difference in post-exposure activity did not correlate with a difference in gene expression during infection or a differential magnitude or quality of the vaccine-specific CD4 T cells induced by ESAT-6 versus TB10.4-containing vaccines. The post-exposure effect of the ESAT-6 based vaccines was found to be influenced by the infectious load at the time-point of vaccination and was abolished in chronically infected animals with high bacterial loads at the onset of vaccination. Our data demonstrate that there are specific requirements for the immune system to target an already established tuberculosis infection and that ESAT-6 has a unique potential in post-exposure vaccination strategies.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Peter Andersen, Else Marie Agger, Carina Vingsbo Lundberg, Gary K Schoolnik, Gregory Dolganov, Joseph P Cassidy, Jes Dietrich, Claus Aagaard, Truc Hoang

Experts in our system

1
Peter Andersen
University College Dublin
Total Publications: 6
 
2
Else Marie Agger
University College Dublin
Total Publications: 4
 
3
Joseph P. Cassidy
University College Dublin
Total Publications: 55
 
4
Jes Dietrich
University College Dublin
Total Publications: 3