Advanced search
1 file | 865.91 KB

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, Erica Houthuys (UGent) , Evelyn Plets (UGent) , Dieter Vanderschaeghe (UGent) , Bram Laukens (UGent) , Bob Asselbergh (UGent) , Eef Parthoens (UGent) , Riet De Rycke (UGent) , et al.
(2011) EMBO MOLECULAR MEDICINE. 3(4). p.222-234
Author
Organization
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.
Keywords
BCG, PULMONARY TUBERCULOSIS, Mycobacterium, SapM, tuberculosis, vaccine, IMMUNE-RESPONSE, DENDRITIC CELLS, MICE, LIPOARABINOMANNAN, INFECTION, CHALLENGE, SURVIVAL, MACROPHAGES, BACILLUS-CALMETTE-GUERIN

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 865.91 KB

Citation

Please use this url to cite or link to this publication:

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.
@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},
}

Altmetric
View in Altmetric
Web of Science
Times cited: