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Immunization with heat-killed Mycobacterium bovis bacille Calmette-Guerin (BCG) in Eurocine L3 adjuvant protects against tuberculosis

Haile, M ; Schröder, U ; Hamasur, B ; Pawlowski, A LU ; Jaxmar, T LU orcid ; Källenius, G and Svenson, S B (2004) In Vaccine 22(11-12). p.508-1498
Abstract

The current live attenuated vaccine against tuberculosis, BCG, poses a risk of disseminated infections in immunocompromised subjects. Therefore, in this study we compared the protective effect of a heat-killed bacille Calmette-Guerin (H-kBCG) vaccine given in a new adjuvant (Eurocine L3) with the protection provided by the conventional live attenuated BCG vaccine in mice (C57BL/6 and BALB/c) challenged with virulent Mycobacterium tuberculosis (strain Harlingen). The H-kBCG vaccine alone, in accordance with earlier studies, did not give any or only gave slight protection compared to sham-vaccinated controls. However, the same vaccine given with Eurocine L3 adjuvant, either formulated as a suspension or as an emulsion, afforded... (More)

The current live attenuated vaccine against tuberculosis, BCG, poses a risk of disseminated infections in immunocompromised subjects. Therefore, in this study we compared the protective effect of a heat-killed bacille Calmette-Guerin (H-kBCG) vaccine given in a new adjuvant (Eurocine L3) with the protection provided by the conventional live attenuated BCG vaccine in mice (C57BL/6 and BALB/c) challenged with virulent Mycobacterium tuberculosis (strain Harlingen). The H-kBCG vaccine alone, in accordance with earlier studies, did not give any or only gave slight protection compared to sham-vaccinated controls. However, the same vaccine given with Eurocine L3 adjuvant, either formulated as a suspension or as an emulsion, afforded significant levels of protection. This protection was at least as good as that of the control live attenuated BCG vaccine. The Eurocine L3 adjuvant is approved for human use as a nasal vaccine adjuvant and a successful phase I trial with nasal immunization with diphtheria vaccine has recently been performed in Sweden. Here we show that, in mice, intranasal priming with H-kBCG in Eurocine L3 adjuvant followed by intranasal booster resulted in the same level of protection as subcutaneous priming followed by intranasal booster. All H-kBCG formulations in the Eurocine L3 adjuvant elicited mycobacterial antigen-specific serum IgG and IFN gamma responses. In general, among the different vaccine formulation(s) in the Eurocine L3 adjuvant those that produced a relatively high Th2 response, as measured by IgG1/IgG2a ratio and IFN gamma production in vitro, were the most protective. In conclusion, H-kBCG in Eurocine L3 adjuvant could represent a safe and a more stable alternative to the conventional live BCG vaccine.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adjuvants, Immunologic, Administration, Intranasal, Animals, BCG Vaccine/administration & dosage, Body Weight, Chemistry, Pharmaceutical, Drug Delivery Systems, Emulsions, Female, Immunization, Secondary, Immunoglobulin G/biosynthesis, Injections, Subcutaneous, Interferon-gamma/biosynthesis, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Survival Analysis, Tuberculosis/prevention & control, Vaccines, Inactivated/immunology
in
Vaccine
volume
22
issue
11-12
pages
508 - 1498
publisher
Elsevier
external identifiers
  • scopus:1842509011
  • pmid:15063575
ISSN
0264-410X
DOI
10.1016/j.vaccine.2003.10.016
language
English
LU publication?
no
id
56b8be44-b28a-4f46-b908-abb065fc0903
date added to LUP
2023-11-16 10:04:19
date last changed
2024-04-14 17:39:23
@article{56b8be44-b28a-4f46-b908-abb065fc0903,
  abstract     = {{<p>The current live attenuated vaccine against tuberculosis, BCG, poses a risk of disseminated infections in immunocompromised subjects. Therefore, in this study we compared the protective effect of a heat-killed bacille Calmette-Guerin (H-kBCG) vaccine given in a new adjuvant (Eurocine L3) with the protection provided by the conventional live attenuated BCG vaccine in mice (C57BL/6 and BALB/c) challenged with virulent Mycobacterium tuberculosis (strain Harlingen). The H-kBCG vaccine alone, in accordance with earlier studies, did not give any or only gave slight protection compared to sham-vaccinated controls. However, the same vaccine given with Eurocine L3 adjuvant, either formulated as a suspension or as an emulsion, afforded significant levels of protection. This protection was at least as good as that of the control live attenuated BCG vaccine. The Eurocine L3 adjuvant is approved for human use as a nasal vaccine adjuvant and a successful phase I trial with nasal immunization with diphtheria vaccine has recently been performed in Sweden. Here we show that, in mice, intranasal priming with H-kBCG in Eurocine L3 adjuvant followed by intranasal booster resulted in the same level of protection as subcutaneous priming followed by intranasal booster. All H-kBCG formulations in the Eurocine L3 adjuvant elicited mycobacterial antigen-specific serum IgG and IFN gamma responses. In general, among the different vaccine formulation(s) in the Eurocine L3 adjuvant those that produced a relatively high Th2 response, as measured by IgG1/IgG2a ratio and IFN gamma production in vitro, were the most protective. In conclusion, H-kBCG in Eurocine L3 adjuvant could represent a safe and a more stable alternative to the conventional live BCG vaccine.</p>}},
  author       = {{Haile, M and Schröder, U and Hamasur, B and Pawlowski, A and Jaxmar, T and Källenius, G and Svenson, S B}},
  issn         = {{0264-410X}},
  keywords     = {{Adjuvants, Immunologic; Administration, Intranasal; Animals; BCG Vaccine/administration & dosage; Body Weight; Chemistry, Pharmaceutical; Drug Delivery Systems; Emulsions; Female; Immunization, Secondary; Immunoglobulin G/biosynthesis; Injections, Subcutaneous; Interferon-gamma/biosynthesis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Survival Analysis; Tuberculosis/prevention & control; Vaccines, Inactivated/immunology}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{11-12}},
  pages        = {{508--1498}},
  publisher    = {{Elsevier}},
  series       = {{Vaccine}},
  title        = {{Immunization with heat-killed Mycobacterium bovis bacille Calmette-Guerin (BCG) in Eurocine L3 adjuvant protects against tuberculosis}},
  url          = {{http://dx.doi.org/10.1016/j.vaccine.2003.10.016}},
  doi          = {{10.1016/j.vaccine.2003.10.016}},
  volume       = {{22}},
  year         = {{2004}},
}