A putative exosporium lipoprotein GBAA0190 of Bacillus anthracis as a potential anthrax vaccine candidate.
Animals
Anthrax
/ prevention & control
Anthrax Vaccines
/ administration & dosage
Bacillus anthracis
/ immunology
Cytokines
/ metabolism
Guinea Pigs
Immunization
Lipoproteins
/ administration & dosage
Macrophages
/ immunology
Mice
Mitogen-Activated Protein Kinases
/ metabolism
NF-kappa B
/ metabolism
Recombinant Proteins
/ administration & dosage
Signal Transduction
Spores, Bacterial
/ immunology
Toll-Like Receptors
/ metabolism
Anthrax
Bacillus anthracis
Exosporium lipoprotein
Vaccine
Journal
BMC immunology
ISSN: 1471-2172
Titre abrégé: BMC Immunol
Pays: England
ID NLM: 100966980
Informations de publication
Date de publication:
21 03 2021
21 03 2021
Historique:
received:
20
11
2020
accepted:
10
03
2021
entrez:
21
3
2021
pubmed:
22
3
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Bacillus ancthracis causes cutaneous, pulmonary, or gastrointestinal forms of anthrax. B. anthracis is a pathogenic bacterium that is potentially to be used in bioterrorism because it can be produced in the form of spores. Currently, protective antigen (PA)-based vaccines are being used for the prevention of anthrax, but it is necessary to develop more safe and effective vaccines due to their prolonged immunization schedules and adverse reactions. We selected the lipoprotein GBAA0190, a potent inducer of host immune response, present in anthrax spores as a novel potential vaccine candidate. Then, we evaluated its immune-stimulating activity in the bone marrow-derived macrophages (BMDMs) using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Protective efficacy of GBAA0190 was evaluated in the guinea pig (GP) model. The recombinant GBAA0190 (r0190) protein induced the expression of various inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in the BMDMs. These immune responses were mediated through toll-like receptor 1/2 via activation of mitogen-activated protein (MAP) kinase and Nuclear factor-κB (NF-κB) pathways. We demonstrated that not only immunization of r0190 alone, but also combined immunization with r0190 and recombinant PA showed significant protective efficacy against B. anthracis spore challenges in the GP model. Our results suggest that r0190 may be a potential target for anthrax vaccine.
Sections du résumé
BACKGROUND
Bacillus ancthracis causes cutaneous, pulmonary, or gastrointestinal forms of anthrax. B. anthracis is a pathogenic bacterium that is potentially to be used in bioterrorism because it can be produced in the form of spores. Currently, protective antigen (PA)-based vaccines are being used for the prevention of anthrax, but it is necessary to develop more safe and effective vaccines due to their prolonged immunization schedules and adverse reactions.
METHODS
We selected the lipoprotein GBAA0190, a potent inducer of host immune response, present in anthrax spores as a novel potential vaccine candidate. Then, we evaluated its immune-stimulating activity in the bone marrow-derived macrophages (BMDMs) using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Protective efficacy of GBAA0190 was evaluated in the guinea pig (GP) model.
RESULTS
The recombinant GBAA0190 (r0190) protein induced the expression of various inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in the BMDMs. These immune responses were mediated through toll-like receptor 1/2 via activation of mitogen-activated protein (MAP) kinase and Nuclear factor-κB (NF-κB) pathways. We demonstrated that not only immunization of r0190 alone, but also combined immunization with r0190 and recombinant PA showed significant protective efficacy against B. anthracis spore challenges in the GP model.
CONCLUSIONS
Our results suggest that r0190 may be a potential target for anthrax vaccine.
Identifiants
pubmed: 33743606
doi: 10.1186/s12865-021-00414-y
pii: 10.1186/s12865-021-00414-y
pmc: PMC7981958
doi:
Substances chimiques
Anthrax Vaccines
0
Cytokines
0
Lipoproteins
0
NF-kappa B
0
Recombinant Proteins
0
Toll-Like Receptors
0
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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