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Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis

Nele Festjens UGent, Pieter Bogaert UGent, Anjana Batni UGent, Erica Houthuys UGent, Evelyn Plets UGent, Dieter Vanderschaeghe UGent, Bram Laukens UGent, Bob Asselbergh UGent, Eef Parthoens UGent and Riet De Rycke UGent, et al. (2011) EMBO MOLECULAR MEDICINE. 3(4). p.222-234
abstract
Mycobacterium bovis bacille Calmette-Guerin (BCG) provides only limited protection against pulmonary tuberculosis. We tested the hypothesis that BCG might have retained immunomodulatory properties from its pathogenic parent that limit its protective immunogenicity. Mutation of the molecules involved in immunomodulation might then improve its vaccine potential. We studied the vaccine potential of BCG mutants deficient in the secreted acid phosphatase, SapM, or in the capping of the innmunomodulatory ManLAM cell wall component with alpha-1,2-oligomannoside. Both systemic and intratracheal challenge of mice with Mycobacterium tuberculosis following vaccination showed that the SapM mutant, compared to the parental BCG vaccine, provided better protection: it led to longer-term survival. Persistence of the SapM-mutated BCG in vivo resembled that of the parental BCG indicating that this mutation will likely not compromise the safety of the BCG vaccine. The SapM mutant BCG vaccine was more effective than the parental vaccine in inducing recruitment and activation of CD11c(+)MHC-II(int)CD4(int) dendritic cells (DCs) to the draining lymph nodes. Thus, SapM acts by inhibiting recruitment of DCs and their activation at the site of vaccination.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
BCG, PULMONARY TUBERCULOSIS, Mycobacterium, SapM, tuberculosis, vaccine, IMMUNE-RESPONSE, DENDRITIC CELLS, MICE, LIPOARABINOMANNAN, INFECTION, CHALLENGE, SURVIVAL, MACROPHAGES, BACILLUS-CALMETTE-GUERIN
journal title
EMBO MOLECULAR MEDICINE
EMBO Mol. Med.
volume
3
issue
4
pages
222 - 234
Web of Science type
Article
Web of Science id
000290011700007
JCR category
MEDICINE, RESEARCH & EXPERIMENTAL
JCR impact factor
10.333 (2011)
JCR rank
6/109 (2011)
JCR quartile
1 (2011)
ISSN
1757-4676
DOI
10.1002/emmm.201000125
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1224438
handle
http://hdl.handle.net/1854/LU-1224438
date created
2011-05-16 14:18:19
date last changed
2012-06-26 14:32:19
@article{1224438,
  abstract     = {Mycobacterium bovis bacille Calmette-Guerin (BCG) provides only limited protection against pulmonary tuberculosis. We tested the hypothesis that BCG might have retained immunomodulatory properties from its pathogenic parent that limit its protective immunogenicity. Mutation of the molecules involved in immunomodulation might then improve its vaccine potential. We studied the vaccine potential of BCG mutants deficient in the secreted acid phosphatase, SapM, or in the capping of the innmunomodulatory ManLAM cell wall component with alpha-1,2-oligomannoside. Both systemic and intratracheal challenge of mice with Mycobacterium tuberculosis following vaccination showed that the SapM mutant, compared to the parental BCG vaccine, provided better protection: it led to longer-term survival. Persistence of the SapM-mutated BCG in vivo resembled that of the parental BCG indicating that this mutation will likely not compromise the safety of the BCG vaccine. The SapM mutant BCG vaccine was more effective than the parental vaccine in inducing recruitment and activation of CD11c(+)MHC-II(int)CD4(int) dendritic cells (DCs) to the draining lymph nodes. Thus, SapM acts by inhibiting recruitment of DCs and their activation at the site of vaccination.},
  author       = {Festjens, Nele and Bogaert, Pieter and Batni, Anjana and Houthuys, Erica and Plets, Evelyn and Vanderschaeghe, Dieter and Laukens, Bram and Asselbergh, Bob and Parthoens, Eef and De Rycke, Riet and Willart, Monique and Jacques, Peggy and Elewaut, Dirk and Brouckaert, Peter and Lambrecht, Bart and Huygen, Kris and Callewaert, Nico},
  issn         = {1757-4676},
  journal      = {EMBO MOLECULAR MEDICINE},
  keyword      = {BCG,PULMONARY TUBERCULOSIS,Mycobacterium,SapM,tuberculosis,vaccine,IMMUNE-RESPONSE,DENDRITIC CELLS,MICE,LIPOARABINOMANNAN,INFECTION,CHALLENGE,SURVIVAL,MACROPHAGES,BACILLUS-CALMETTE-GUERIN},
  language     = {eng},
  number       = {4},
  pages        = {222--234},
  title        = {Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis},
  url          = {http://dx.doi.org/10.1002/emmm.201000125},
  volume       = {3},
  year         = {2011},
}

Chicago
Festjens, Nele, Pieter Bogaert, Anjana Batni, Erica Houthuys, Evelyn Plets, Dieter Vanderschaeghe, Bram Laukens, et al. 2011. “Disruption of the SapM Locus in Mycobacterium Bovis BCG Improves Its Protective Efficacy as a Vaccine Against M. Tuberculosis.” Embo Molecular Medicine 3 (4): 222–234.
APA
Festjens, N., Bogaert, P., Batni, A., Houthuys, E., Plets, E., Vanderschaeghe, D., Laukens, B., et al. (2011). Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis. EMBO MOLECULAR MEDICINE, 3(4), 222–234.
Vancouver
1.
Festjens N, Bogaert P, Batni A, Houthuys E, Plets E, Vanderschaeghe D, et al. Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis. EMBO MOLECULAR MEDICINE. 2011;3(4):222–34.
MLA
Festjens, Nele, Pieter Bogaert, Anjana Batni, et al. “Disruption of the SapM Locus in Mycobacterium Bovis BCG Improves Its Protective Efficacy as a Vaccine Against M. Tuberculosis.” EMBO MOLECULAR MEDICINE 3.4 (2011): 222–234. Print.