A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains

dc.creatorZurita, María Eugenia
dc.creatorWilk, Mieszko M.
dc.creatorCarriquiriborde, Francisco Pablo
dc.creatorBartel, Erika Belén
dc.creatorMoreno, Griselda
dc.creatorMisiak, Alicja
dc.creatorMills, Kingston H. G.
dc.creatorHozbor, Daniela Flavia
dc.date2019
dc.date2020-10-19T16:15:50Z
dc.date.accessioned2023-07-14T22:43:53Z
dc.date.available2023-07-14T22:43:53Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/107279
dc.identifierhttp://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6498398&blobtype=pdf
dc.identifierissn:2235-2988
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7447995
dc.descriptionPertussis 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.
dc.descriptionInstituto de Biotecnologia y Biologia Molecular
dc.descriptionInstituto de Estudios Inmunológicos y Fisiopatológicos
dc.formatapplication/pdf
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by/4.0/
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)
dc.subjectBiología
dc.subjectBordetella pertussis
dc.subjectPertussis
dc.subjectOuter membrane vesicles
dc.subjectTRM cells
dc.subjectPertactin deficient strains
dc.subjectProtection
dc.titleA Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains
dc.typeArticulo
dc.typeArticulo


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