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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Detalles Bibliográficos
Autores principales: Zurita, María Eugenia, Wilk, Mieszko M., Carriquiriborde, Francisco Pablo, Bartel, Erika Belén, Moreno, Griselda, Misiak, Alicja, Mills, Kingston H. G., Hozbor, Daniela Flavia
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
Materias:
Biología
Bordetella pertussis
Pertussis
Outer membrane vesicles
TRM cells
Pertactin deficient strains
Protection
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107279
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6498398&blobtype=pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-107279
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Bordetella pertussis
Pertussis
Outer membrane vesicles
TRM cells
Pertactin deficient strains
Protection
spellingShingle Biología
Bordetella pertussis
Pertussis
Outer membrane vesicles
TRM cells
Pertactin deficient strains
Protection
Zurita, María Eugenia
Wilk, Mieszko M.
Carriquiriborde, Francisco Pablo
Bartel, Erika Belén
Moreno, Griselda
Misiak, Alicja
Mills, Kingston H. G.
Hozbor, Daniela Flavia
A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains
topic_facet Biología
Bordetella pertussis
Pertussis
Outer membrane vesicles
TRM cells
Pertactin deficient strains
Protection
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.
format Articulo
Articulo
author Zurita, María Eugenia
Wilk, Mieszko M.
Carriquiriborde, Francisco Pablo
Bartel, Erika Belén
Moreno, Griselda
Misiak, Alicja
Mills, Kingston H. G.
Hozbor, Daniela Flavia
author_facet Zurita, María Eugenia
Wilk, Mieszko M.
Carriquiriborde, Francisco Pablo
Bartel, Erika Belén
Moreno, Griselda
Misiak, Alicja
Mills, Kingston H. G.
Hozbor, Daniela Flavia
author_sort Zurita, María Eugenia
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
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/107279
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6498398&blobtype=pdf
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