A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains
Pertussis is a respiratory infectious disease that has been resurged during the last decades. The change from the traditional multi-antigen whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines that consist of a few antigens formulated with alum, appears to be a key factor in the r...
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Frontiers Media S.A.
2019-04-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2019.00125/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
María Eugenia Zurita Mieszko M. Wilk Francisco Carriquiriborde Erika Bartel Griselda Moreno Alicja Misiak Kingston H. G. Mills Daniela Hozbor |
spellingShingle |
María Eugenia Zurita Mieszko M. Wilk Francisco Carriquiriborde Erika Bartel Griselda Moreno Alicja Misiak Kingston H. G. Mills Daniela Hozbor A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains Frontiers in Cellular and Infection Microbiology Bordetella pertussis pertussis outer membrane vesicles TRM cells pertactin deficient strains protection |
author_facet |
María Eugenia Zurita Mieszko M. Wilk Francisco Carriquiriborde Erika Bartel Griselda Moreno Alicja Misiak Kingston H. G. Mills Daniela Hozbor |
author_sort |
María Eugenia Zurita |
title |
A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains |
title_short |
A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains |
title_full |
A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains |
title_fullStr |
A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains |
title_full_unstemmed |
A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains |
title_sort |
pertussis outer membrane vesicle-based vaccine induces lung-resident memory cd4 t cells and protection against bordetella pertussis, including pertactin deficient strains |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2019-04-01 |
description |
Pertussis is a respiratory infectious disease that has been resurged during the last decades. The change from the traditional multi-antigen whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines that consist of a few antigens formulated with alum, appears to be a key factor in the resurgence of pertussis in many countries. Though current aP vaccines have helped to reduce the morbidity and mortality associated with pertussis, they do not provide durable immunity or adequate protection against the disease caused by the current circulating strains of Bordetella pertussis, which have evolved in the face of the selection pressure induced by the vaccines. Based on the hypothesis that a new vaccine containing multiple antigens could overcome deficiencies in the current aP vaccines, we have designed and characterized a vaccine candidate based on outer membrane vesicle (OMVs). Here we show that the OMVs vaccine, but not an aP vaccine, protected mice against lung infection with a circulating pertactin (PRN)-deficient isolate. Using isogenic bacteria that in principle only differ in PRN expression, we found that deficiency in PRN appears to be largely responsible for the failure of the aP vaccine to protect against this circulating clinical isolates. Regarding the durability of induced immunity, we have already reported that the OMV vaccine is able to induce long-lasting immune responses that effectively prevent infection with B. pertussis. Consistent with this, here we found that CD4 T cells with a tissue-resident memory (TRM) cell phenotype (CD44+CD62LlowCD69+ and/or CD103+) accumulated in the lungs of mice 14 days after immunization with 2 doses of the OMVs vaccine. CD4 TRM cells, which have previously been shown to play a critical role sustained protective immunity against B. pertussis, were also detected in mice immunized with wP vaccine, but not in the animals immunized with a commercial aP vaccine. The CD4 TRM cells secreted IFN-γ and IL-17 and were significantly expanded through local proliferation following respiratory challenge of mice with B. pertussis. Our findings that the OMVs vaccine induce respiratory CD4 TRM cells may explain the ability of this vaccine to induce long-term protection and is therefore an ideal candidate for a third generation vaccine against B. pertussis. |
topic |
Bordetella pertussis pertussis outer membrane vesicles TRM cells pertactin deficient strains protection |
url |
https://www.frontiersin.org/article/10.3389/fcimb.2019.00125/full |
work_keys_str_mv |
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doaj-fc43ae6ab3b04ca0904e818d4d05b3f12020-11-25T01:22:19ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882019-04-01910.3389/fcimb.2019.00125441689A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient StrainsMaría Eugenia Zurita0Mieszko M. Wilk1Francisco Carriquiriborde2Erika Bartel3Griselda Moreno4Alicja Misiak5Kingston H. G. Mills6Daniela Hozbor7Laboratorio VacSal, Facultad de Ciencias Exactas, Instituto de Biotecnología y Biología Molecular (IBBM), CCT-CONICET La Plata, Universidad Nacional de La Plata, La Plata, ArgentinaSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandLaboratorio VacSal, Facultad de Ciencias Exactas, Instituto de Biotecnología y Biología Molecular (IBBM), CCT-CONICET La Plata, Universidad Nacional de La Plata, La Plata, ArgentinaLaboratorio VacSal, Facultad de Ciencias Exactas, Instituto de Biotecnología y Biología Molecular (IBBM), CCT-CONICET La Plata, Universidad Nacional de La Plata, La Plata, ArgentinaFacultad de Ciencias Exactas, Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CCT-CONICET La Plata, Universidad Nacional de La Plata, La Plata, ArgentinaSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandLaboratorio VacSal, Facultad de Ciencias Exactas, Instituto de Biotecnología y Biología Molecular (IBBM), CCT-CONICET La Plata, Universidad Nacional de La Plata, La Plata, ArgentinaPertussis is a respiratory infectious disease that has been resurged during the last decades. The change from the traditional multi-antigen whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines that consist of a few antigens formulated with alum, appears to be a key factor in the resurgence of pertussis in many countries. Though current aP vaccines have helped to reduce the morbidity and mortality associated with pertussis, they do not provide durable immunity or adequate protection against the disease caused by the current circulating strains of Bordetella pertussis, which have evolved in the face of the selection pressure induced by the vaccines. Based on the hypothesis that a new vaccine containing multiple antigens could overcome deficiencies in the current aP vaccines, we have designed and characterized a vaccine candidate based on outer membrane vesicle (OMVs). Here we show that the OMVs vaccine, but not an aP vaccine, protected mice against lung infection with a circulating pertactin (PRN)-deficient isolate. Using isogenic bacteria that in principle only differ in PRN expression, we found that deficiency in PRN appears to be largely responsible for the failure of the aP vaccine to protect against this circulating clinical isolates. Regarding the durability of induced immunity, we have already reported that the OMV vaccine is able to induce long-lasting immune responses that effectively prevent infection with B. pertussis. Consistent with this, here we found that CD4 T cells with a tissue-resident memory (TRM) cell phenotype (CD44+CD62LlowCD69+ and/or CD103+) accumulated in the lungs of mice 14 days after immunization with 2 doses of the OMVs vaccine. CD4 TRM cells, which have previously been shown to play a critical role sustained protective immunity against B. pertussis, were also detected in mice immunized with wP vaccine, but not in the animals immunized with a commercial aP vaccine. The CD4 TRM cells secreted IFN-γ and IL-17 and were significantly expanded through local proliferation following respiratory challenge of mice with B. pertussis. Our findings that the OMVs vaccine induce respiratory CD4 TRM cells may explain the ability of this vaccine to induce long-term protection and is therefore an ideal candidate for a third generation vaccine against B. pertussis.https://www.frontiersin.org/article/10.3389/fcimb.2019.00125/fullBordetella pertussispertussisouter membrane vesiclesTRM cellspertactin deficient strainsprotection |