Dual mechanism of protection by live attenuated Bordetella pertussis BPZE1 against Bordetella bronchiseptica in mice

Highlights ► Live attenuated B. pertussis BPZE1 protects against B. bronchiseptica . ► BPZE1-induced protection is due to a dual cell-mediated immune mechanism. ► Both effector cells and regulatory T cells participate in protection.

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Bibliographic Details
Published inVaccine Vol. 30; no. 40; pp. 5864 - 5870
Main Authors Kammoun, Hana, Feunou, Pascal Feunou, Foligne, Benoit, Debrie, Anne-Sophie, Raze, Dominique, Mielcarek, Nathalie, Locht, Camille
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 31.08.2012
Subjects
Administration, Intranasal
Adoptive Transfer
Allergy and Immunology
Animals
Antibodies
Antibodies, Bacterial - blood
antigens
Bacterial Load
Bordetella bronchiseptica
Bordetella bronchiseptica - immunology
Bordetella Infections - immunology
Bordetella Infections - prevention & control
Bordetella parapertussis
Bordetella pertussis
Bordetella pertussis - immunology
CD25 antigen
CD4 antigen
Chronic infection
Clinical trials
Cytokines - immunology
Female
Foxp3 protein
Gram-negative bacteria
Helper cells
hosts
humans
Immunity, Cellular
Immunization - methods
Immunoregulation
Inflammation
Intranasal administration
Leukocytes (neutrophilic)
Lung
Lung - immunology
lungs
Lymphocytes B
Lymphocytes T
Mice
Mice, Inbred BALB C
Mice, SCID
neutrophils
Pertussis
Pertussis Vaccine - immunology
pneumonia
Pneumonia - immunology
Pneumonia - microbiology
recruitment
Regulatory T cells
Respiratory tract diseases
T-lymphocytes
T-Lymphocytes, Regulatory - immunology
Th1 Cells - immunology
Th17 Cells - immunology
Vaccine
Vaccines
Vaccines, Attenuated - immunology
Bordetella bronchiseptica
Vaccine
Bordetella pertussis
Regulatory T cells
Online AccessGet full text

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Abstract Highlights ► Live attenuated B. pertussis BPZE1 protects against B. bronchiseptica . ► BPZE1-induced protection is due to a dual cell-mediated immune mechanism. ► Both effector cells and regulatory T cells participate in protection.
AbstractList Bordetella bronchiseptica, a gram-negative bacterium, causes chronic respiratory tract infections in a wide variety of mammalian hosts, including man, and no human vaccine is currently available. Acellular pertussis vaccines protect poorly against B. bronchiseptica, although they contain cross-reactive antigens. We have recently developed Bordetella pertussis BPZE1, a novel, live attenuated pertussis vaccine, currently completing phase I clinical trials in humans, and found that it protects against both B. pertussis and Bordetella parapertussis in mice. Here, we show that a single nasal administration of BPZE1 protects mice against lethal infection with B. bronchiseptica. After challenge, the vaccinated animals displayed markedly reduced lung inflammation and tissue damage, decreased neutrophil infiltration and increased levels of CD4+CD25+FoxP3+ regulatory T cells in the lungs compared to non-immunized mice. Depletion of these cells abolished BPZE1-induced protection, indicating that BPZE1 protects against lethal inflammation through the recruitment of regulatory T cells. In addition, the B. bronchiseptica load was significantly decreased in the vaccinated animals. Using passive transfer experiments, protection was found to be essentially cell mediated, and BPZE1-induced Th1 and Th17 T cells recognize whole B. bronchiseptica extracts, although the participation of antibodies in protection cannot be discounted. Thus, a single administration of BPZE1 can confer protection against B. bronchiseptica in mice by a dual mechanism.
► Live attenuated B. pertussis BPZE1 protects against B. bronchiseptica. ► BPZE1-induced protection is due to a dual cell-mediated immune mechanism. ► Both effector cells and regulatory T cells participate in protection. Bordetella bronchiseptica, a gram-negative bacterium, causes chronic respiratory tract infections in a wide variety of mammalian hosts, including man, and no human vaccine is currently available. Acellular pertussis vaccines protect poorly against B. bronchiseptica, although they contain cross-reactive antigens. We have recently developed Bordetella pertussis BPZE1, a novel, live attenuated pertussis vaccine, currently completing phase I clinical trials in humans, and found that it protects against both B. pertussis and Bordetella parapertussis in mice. Here, we show that a single nasal administration of BPZE1 protects mice against lethal infection with B. bronchiseptica. After challenge, the vaccinated animals displayed markedly reduced lung inflammation and tissue damage, decreased neutrophil infiltration and increased levels of CD4+CD25+FoxP3+ regulatory T cells in the lungs compared to non-immunized mice. Depletion of these cells abolished BPZE1-induced protection, indicating that BPZE1 protects against lethal inflammation through the recruitment of regulatory T cells. In addition, the B. bronchiseptica load was significantly decreased in the vaccinated animals. Using passive transfer experiments, protection was found to be essentially cell mediated, and BPZE1-induced Th1 and Th17 T cells recognize whole B. bronchiseptica extracts, although the participation of antibodies in protection cannot be discounted. Thus, a single administration of BPZE1 can confer protection against B. bronchiseptica in mice by a dual mechanism.
Highlights ► Live attenuated B. pertussis BPZE1 protects against B. bronchiseptica . ► BPZE1-induced protection is due to a dual cell-mediated immune mechanism. ► Both effector cells and regulatory T cells participate in protection.
Bordetella bronchiseptica, a gram-negative bacterium, causes chronic respiratory tract infections in a wide variety of mammalian hosts, including man, and no human vaccine is currently available. Acellular pertussis vaccines protect poorly against B. bronchiseptica, although they contain cross-reactive antigens. We have recently developed Bordetella pertussis BPZE1, a novel, live attenuated pertussis vaccine, currently completing phase I clinical trials in humans, and found that it protects against both B. pertussis and Bordetella parapertussis in mice. Here, we show that a single nasal administration of BPZE1 protects mice against lethal infection with B. bronchiseptica. After challenge, the vaccinated animals displayed markedly reduced lung inflammation and tissue damage, decreased neutrophil infiltration and increased levels of CD4⁺CD25⁺FoxP3⁺ regulatory T cells in the lungs compared to non-immunized mice. Depletion of these cells abolished BPZE1-induced protection, indicating that BPZE1 protects against lethal inflammation through the recruitment of regulatory T cells. In addition, the B. bronchiseptica load was significantly decreased in the vaccinated animals. Using passive transfer experiments, protection was found to be essentially cell mediated, and BPZE1-induced Th1 and Th17 T cells recognize whole B. bronchiseptica extracts, although the participation of antibodies in protection cannot be discounted. Thus, a single administration of BPZE1 can confer protection against B. bronchiseptica in mice by a dual mechanism.
Author Mielcarek, Nathalie
Foligne, Benoit
Debrie, Anne-Sophie
Kammoun, Hana
Locht, Camille
Raze, Dominique
Feunou, Pascal Feunou
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Keywords Bordetella bronchiseptica
Vaccine
Bordetella pertussis
Regulatory T cells
Language English
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Snippet Highlights ► Live attenuated B. pertussis BPZE1 protects against B. bronchiseptica . ► BPZE1-induced protection is due to a dual cell-mediated immune...
► Live attenuated B. pertussis BPZE1 protects against B. bronchiseptica. ► BPZE1-induced protection is due to a dual cell-mediated immune mechanism. ► Both...
Bordetella bronchiseptica, a gram-negative bacterium, causes chronic respiratory tract infections in a wide variety of mammalian hosts, including man, and no...
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SubjectTerms Administration, Intranasal
Adoptive Transfer
Allergy and Immunology
Animals
Antibodies
Antibodies, Bacterial - blood
antigens
Bacterial Load
Bordetella bronchiseptica
Bordetella bronchiseptica - immunology
Bordetella Infections - immunology
Bordetella Infections - prevention & control
Bordetella parapertussis
Bordetella pertussis
Bordetella pertussis - immunology
CD25 antigen
CD4 antigen
Chronic infection
Clinical trials
Cytokines - immunology
Female
Foxp3 protein
Gram-negative bacteria
Helper cells
hosts
humans
Immunity, Cellular
Immunization - methods
Immunoregulation
Inflammation
Intranasal administration
Leukocytes (neutrophilic)
Lung
Lung - immunology
lungs
Lymphocytes B
Lymphocytes T
Mice
Mice, Inbred BALB C
Mice, SCID
neutrophils
Pertussis
Pertussis Vaccine - immunology
pneumonia
Pneumonia - immunology
Pneumonia - microbiology
recruitment
Regulatory T cells
Respiratory tract diseases
T-lymphocytes
T-Lymphocytes, Regulatory - immunology
Th1 Cells - immunology
Th17 Cells - immunology
Vaccine
Vaccines
Vaccines, Attenuated - immunology
Title Dual mechanism of protection by live attenuated Bordetella pertussis BPZE1 against Bordetella bronchiseptica in mice
URI https://www.clinicalkey.es/playcontent/1-s2.0-S0264410X12010067
https://dx.doi.org/10.1016/j.vaccine.2012.07.005
https://www.ncbi.nlm.nih.gov/pubmed/22814407
https://search.proquest.com/docview/1033454362
https://search.proquest.com/docview/1038606007
Volume 30
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