TY - JOUR
T1 - Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis vaccine
AU - Köster, Stefan
AU - Klevorn, Thais
AU - Papavinasasundaram, Kadamba
AU - Sassetti, Christopher M.
AU - Portal-Celhay, Cynthia
AU - Philips, Jennifer A.
N1 - Funding Information:
We would like to thank N. Mizushima (University of Tokyo) and A. Yamamoto (Columbia University) for providing LC3-GFP expressing mice. M. tuberculosis strains mc 2 6206 and mc 2 6230 were kindly provided by M. Larsen and W. Jacobs (Albert Einstein College of Medicine). We thank J. Ernst (NYU SOM), M. Larsen (Albert Einstein College of Medicine), and the Philips lab for helpful discussions, and C. O’Shaughnessy for help with mouse harvests. This project was supported by the Potts Memorial Foundation , the Stony Wold-Herbert Foundation , NIH/NIAID R01 AI130454 to J.A.P., NIH/NIAID K08 AI119150 and the Doris Duke Charitabe Foundation Fund to Retain Clinical Scientists to C.P.-C, NIH/NIAID R01 AI107774 and AI064282 (to C.M.S.) and the NYU School of Medicine including the Applied Research Support Fund (ARSF).
Funding Information:
We would like to thank N. Mizushima (University of Tokyo) and A. Yamamoto (Columbia University) for providing LC3-GFP expressing mice. M. tuberculosis strains mc26206 and mc26230 were kindly provided by M. Larsen and W. Jacobs (Albert Einstein College of Medicine). We thank J. Ernst (NYU SOM), M. Larsen (Albert Einstein College of Medicine), and the Philips lab for helpful discussions, and C. O'Shaughnessy for help with mouse harvests. This project was supported by the Potts Memorial Foundation, the Stony Wold-Herbert Foundation, NIH/NIAID R01 AI130454 to J.A.P., NIH/NIAID K08 AI119150 and the Doris Duke Charitabe Foundation Fund to Retain Clinical Scientists to C.P.-C, NIH/NIAID R01 AI107774 and AI064282 (to C.M.S.) and the NYU School of Medicine including the Applied Research Support Fund (ARSF).
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/2/8
Y1 - 2018/2/8
N2 - Development of a new vaccine against tuberculosis is urgently needed. Recent work has demonstrated that two related LC3-associated trafficking pathways, autophagy and LC3-associated phagocytosis (LAP), enhance antigen presentation and might play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3-trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3-trafficking than M. tuberculosis, which may help explain its limited efficacy. To determine whether enhanced LC3-trafficking can improve efficacy of a live, attenuated M. tuberculosis vaccine, we took advantage of our recent finding that the bacterial virulence factor CpsA inhibits LAP. When we deleted cpsA in the mc26206 vaccine strain, it dramatically increased LC3-trafficking. We compared the protective efficacy of the strain lacking cpsA to the parent strain and to BCG in mice challenged with M. tuberculosis. We found that the strain lacking cpsA generated modestly enhanced protection in the spleen, but overall did not outperform BCG.
AB - Development of a new vaccine against tuberculosis is urgently needed. Recent work has demonstrated that two related LC3-associated trafficking pathways, autophagy and LC3-associated phagocytosis (LAP), enhance antigen presentation and might play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3-trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3-trafficking than M. tuberculosis, which may help explain its limited efficacy. To determine whether enhanced LC3-trafficking can improve efficacy of a live, attenuated M. tuberculosis vaccine, we took advantage of our recent finding that the bacterial virulence factor CpsA inhibits LAP. When we deleted cpsA in the mc26206 vaccine strain, it dramatically increased LC3-trafficking. We compared the protective efficacy of the strain lacking cpsA to the parent strain and to BCG in mice challenged with M. tuberculosis. We found that the strain lacking cpsA generated modestly enhanced protection in the spleen, but overall did not outperform BCG.
KW - Autophagy
KW - Auxotroph
KW - BCG
KW - Innate immunity
KW - LC3-associated phagocytosis
KW - Live attenuated vaccine
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85040509871&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2018.01.012
DO - 10.1016/j.vaccine.2018.01.012
M3 - Article
C2 - 29343411
AN - SCOPUS:85040509871
VL - 36
SP - 939
EP - 944
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 7
ER -