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Nasal boost with adjuvanted heat-killed BCG or arabinomannan-protein conjugate improves primary BCG-induced protection in C57BL/6 mice

Haile, M ; Hamasur, B ; Jaxmar, T LU orcid ; Gavier-Widen, D ; Chambers, M A ; Sanchez, B ; Schröder, U ; Källenius, G ; Svenson, S B and Pawlowski, A LU (2005) In Tuberculosis 85(1-2). p.14-107
Abstract

Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability of two new TB vaccine candidates, heat-killed BCG (H-kBCG) and arabinomannan-tetanus toxoid conjugate (AM-TT), given intransally in a novel Eurocine adjuvant, to boost a primary BCG-induced immune response and to improve protection. Young C57BL/6 mice were vaccinated with conventional BCG and, 6 months later, boosted intranasally with... (More)

Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability of two new TB vaccine candidates, heat-killed BCG (H-kBCG) and arabinomannan-tetanus toxoid conjugate (AM-TT), given intransally in a novel Eurocine adjuvant, to boost a primary BCG-induced immune response and to improve protection. Young C57BL/6 mice were vaccinated with conventional BCG and, 6 months later, boosted intranasally with adjuvanted H-kBCG or AM-TT, or subcutaneously with BCG. Ten weeks after the booster, mice were challenged intravenously with M. tuberculosis (Mtb) strain H37Rv. In spleens, there was a significant reduction of cfu counts in mice boosted with either H-kBCG or AM-TT vaccines compared to the non-boosted BCG-vaccinated mice. None of the boosting regimens significantly reduced bacterial loads in lungs, compared to non-boosted BCG vaccination. However, the extent of granulomatous inflammation was significantly reduced in the lungs of mice that received two of the booster vaccines (AM-TT and conventional BCG), as compared with sham-vaccinated mice. All boosted groups, except for mice boosted with the AM-TT vaccine, responded with a proliferation of spleen T cells and gamma interferon production comparable to that induced by a single BCG vaccination.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Administration, Intranasal, Animals, BCG Vaccine/administration & dosage, Colony Count, Microbial/methods, Female, Granuloma/immunology, Interferon-gamma/immunology, Lung/microbiology, Mannans/administration & dosage, Mice, Mice, Inbred C57BL, Polysaccharides, Bacterial/administration & dosage, Spleen/microbiology, Tetanus Toxoid/administration & dosage, Tuberculosis Vaccines/administration & dosage, Tuberculosis, Pulmonary/immunology, Vaccination/methods, Vaccines, Conjugate/administration & dosage
in
Tuberculosis
volume
85
issue
1-2
pages
14 - 107
publisher
Elsevier
external identifiers
  • pmid:15687034
  • scopus:20144387363
ISSN
1472-9792
DOI
10.1016/j.tube.2004.09.013
language
English
LU publication?
no
id
5549390f-7993-464d-be7f-b77c92382825
date added to LUP
2023-11-16 10:01:44
date last changed
2024-03-31 15:52:24
@article{5549390f-7993-464d-be7f-b77c92382825,
  abstract     = {{<p>Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability of two new TB vaccine candidates, heat-killed BCG (H-kBCG) and arabinomannan-tetanus toxoid conjugate (AM-TT), given intransally in a novel Eurocine adjuvant, to boost a primary BCG-induced immune response and to improve protection. Young C57BL/6 mice were vaccinated with conventional BCG and, 6 months later, boosted intranasally with adjuvanted H-kBCG or AM-TT, or subcutaneously with BCG. Ten weeks after the booster, mice were challenged intravenously with M. tuberculosis (Mtb) strain H37Rv. In spleens, there was a significant reduction of cfu counts in mice boosted with either H-kBCG or AM-TT vaccines compared to the non-boosted BCG-vaccinated mice. None of the boosting regimens significantly reduced bacterial loads in lungs, compared to non-boosted BCG vaccination. However, the extent of granulomatous inflammation was significantly reduced in the lungs of mice that received two of the booster vaccines (AM-TT and conventional BCG), as compared with sham-vaccinated mice. All boosted groups, except for mice boosted with the AM-TT vaccine, responded with a proliferation of spleen T cells and gamma interferon production comparable to that induced by a single BCG vaccination.</p>}},
  author       = {{Haile, M and Hamasur, B and Jaxmar, T and Gavier-Widen, D and Chambers, M A and Sanchez, B and Schröder, U and Källenius, G and Svenson, S B and Pawlowski, A}},
  issn         = {{1472-9792}},
  keywords     = {{Administration, Intranasal; Animals; BCG Vaccine/administration & dosage; Colony Count, Microbial/methods; Female; Granuloma/immunology; Interferon-gamma/immunology; Lung/microbiology; Mannans/administration & dosage; Mice; Mice, Inbred C57BL; Polysaccharides, Bacterial/administration & dosage; Spleen/microbiology; Tetanus Toxoid/administration & dosage; Tuberculosis Vaccines/administration & dosage; Tuberculosis, Pulmonary/immunology; Vaccination/methods; Vaccines, Conjugate/administration & dosage}},
  language     = {{eng}},
  number       = {{1-2}},
  pages        = {{14--107}},
  publisher    = {{Elsevier}},
  series       = {{Tuberculosis}},
  title        = {{Nasal boost with adjuvanted heat-killed BCG or arabinomannan-protein conjugate improves primary BCG-induced protection in C57BL/6 mice}},
  url          = {{http://dx.doi.org/10.1016/j.tube.2004.09.013}},
  doi          = {{10.1016/j.tube.2004.09.013}},
  volume       = {{85}},
  year         = {{2005}},
}