Cargando…

Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture

Outer membrane vesicles (OMV) derived from Bordetella pertussis—the etiologic agent of the resurgent disease called pertussis—are safe and effective in preventing bacterial colonization in the lungs of immunized mice. Vaccine formulations containing those OMV are capable of inducing a mixed Th1/Th2/...

Descripción completa

Detalles Bibliográficos
Autores principales: Carriquiriborde, Francisco, Martin Aispuro, Pablo, Ambrosis, Nicolás, Zurita, Eugenia, Bottero, Daniela, Gaillard, María Emilia, Castuma, Celina, Rudi, Erika, Lodeiro, Aníbal, Hozbor, Daniela F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479151/
https://www.ncbi.nlm.nih.gov/pubmed/34603306
http://dx.doi.org/10.3389/fimmu.2021.730434
_version_ 1784576188022259712
author Carriquiriborde, Francisco
Martin Aispuro, Pablo
Ambrosis, Nicolás
Zurita, Eugenia
Bottero, Daniela
Gaillard, María Emilia
Castuma, Celina
Rudi, Erika
Lodeiro, Aníbal
Hozbor, Daniela F.
author_facet Carriquiriborde, Francisco
Martin Aispuro, Pablo
Ambrosis, Nicolás
Zurita, Eugenia
Bottero, Daniela
Gaillard, María Emilia
Castuma, Celina
Rudi, Erika
Lodeiro, Aníbal
Hozbor, Daniela F.
author_sort Carriquiriborde, Francisco
collection PubMed
description Outer membrane vesicles (OMV) derived from Bordetella pertussis—the etiologic agent of the resurgent disease called pertussis—are safe and effective in preventing bacterial colonization in the lungs of immunized mice. Vaccine formulations containing those OMV are capable of inducing a mixed Th1/Th2/Th17 profile, but even more interestingly, they may induce a tissue-resident memory immune response. This immune response is recommended for the new generation of pertussis-vaccines that must be developed to overcome the weaknesses of current commercial acellular vaccines (second-generation of pertussis vaccine). The third-generation of pertussis vaccine should also deal with infections caused by bacteria that currently circulate in the population and are phenotypically and genotypically different [in particular those deficient in the expression of pertactin antigen, PRN(-)] from those that circulated in the past. Here we evaluated the protective capacity of OMV derived from bacteria grown in biofilm, since it was observed that, by difference with older culture collection vaccine strains, circulating clinical B. pertussis isolates possess higher capacity for this lifestyle. Therefore, we performed studies with a clinical isolate with good biofilm-forming capacity. Biofilm lifestyle was confirmed by both scanning electron microscopy and proteomics. While scanning electron microscopy revealed typical biofilm structures in these cultures, BipA, fimbria, and other adhesins described as typical of the biofilm lifestyle were overexpressed in the biofilm culture in comparison with planktonic culture. OMV derived from biofilm (OMVbiof) or planktonic lifestyle (OMVplank) were used to formulate vaccines to compare their immunogenicity and protective capacities against infection with PRN(+) or PRN(-) B. pertussis clinical isolates. Using the mouse protection model, we detected that OMVbiof-vaccine was more immunogenic than OMVplank-vaccine in terms of both specific antibody titers and quality, since OMVbiof-vaccine induced antibodies with higher avidity. Moreover, when OMV were administered at suboptimal quantity for protection, OMVbiof-vaccine exhibited a significantly adequate and higher protective capacity against PRN(+) or PRN(-) than OMVplank-vaccine. Our findings indicate that the vaccine based on B. pertussis biofilm-derived OMV induces high protection also against pertactin-deficient strains, with a robust immune response.
format Online
Article
Text
id pubmed-8479151
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-84791512021-09-30 Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture Carriquiriborde, Francisco Martin Aispuro, Pablo Ambrosis, Nicolás Zurita, Eugenia Bottero, Daniela Gaillard, María Emilia Castuma, Celina Rudi, Erika Lodeiro, Aníbal Hozbor, Daniela F. Front Immunol Immunology Outer membrane vesicles (OMV) derived from Bordetella pertussis—the etiologic agent of the resurgent disease called pertussis—are safe and effective in preventing bacterial colonization in the lungs of immunized mice. Vaccine formulations containing those OMV are capable of inducing a mixed Th1/Th2/Th17 profile, but even more interestingly, they may induce a tissue-resident memory immune response. This immune response is recommended for the new generation of pertussis-vaccines that must be developed to overcome the weaknesses of current commercial acellular vaccines (second-generation of pertussis vaccine). The third-generation of pertussis vaccine should also deal with infections caused by bacteria that currently circulate in the population and are phenotypically and genotypically different [in particular those deficient in the expression of pertactin antigen, PRN(-)] from those that circulated in the past. Here we evaluated the protective capacity of OMV derived from bacteria grown in biofilm, since it was observed that, by difference with older culture collection vaccine strains, circulating clinical B. pertussis isolates possess higher capacity for this lifestyle. Therefore, we performed studies with a clinical isolate with good biofilm-forming capacity. Biofilm lifestyle was confirmed by both scanning electron microscopy and proteomics. While scanning electron microscopy revealed typical biofilm structures in these cultures, BipA, fimbria, and other adhesins described as typical of the biofilm lifestyle were overexpressed in the biofilm culture in comparison with planktonic culture. OMV derived from biofilm (OMVbiof) or planktonic lifestyle (OMVplank) were used to formulate vaccines to compare their immunogenicity and protective capacities against infection with PRN(+) or PRN(-) B. pertussis clinical isolates. Using the mouse protection model, we detected that OMVbiof-vaccine was more immunogenic than OMVplank-vaccine in terms of both specific antibody titers and quality, since OMVbiof-vaccine induced antibodies with higher avidity. Moreover, when OMV were administered at suboptimal quantity for protection, OMVbiof-vaccine exhibited a significantly adequate and higher protective capacity against PRN(+) or PRN(-) than OMVplank-vaccine. Our findings indicate that the vaccine based on B. pertussis biofilm-derived OMV induces high protection also against pertactin-deficient strains, with a robust immune response. Frontiers Media S.A. 2021-09-15 /pmc/articles/PMC8479151/ /pubmed/34603306 http://dx.doi.org/10.3389/fimmu.2021.730434 Text en Copyright © 2021 Carriquiriborde, Martin Aispuro, Ambrosis, Zurita, Bottero, Gaillard, Castuma, Rudi, Lodeiro and Hozbor https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Carriquiriborde, Francisco
Martin Aispuro, Pablo
Ambrosis, Nicolás
Zurita, Eugenia
Bottero, Daniela
Gaillard, María Emilia
Castuma, Celina
Rudi, Erika
Lodeiro, Aníbal
Hozbor, Daniela F.
Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture
title Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture
title_full Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture
title_fullStr Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture
title_full_unstemmed Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture
title_short Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture
title_sort pertussis vaccine candidate based on outer membrane vesicles derived from biofilm culture
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479151/
https://www.ncbi.nlm.nih.gov/pubmed/34603306
http://dx.doi.org/10.3389/fimmu.2021.730434
work_keys_str_mv AT carriquiribordefrancisco pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT martinaispuropablo pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT ambrosisnicolas pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT zuritaeugenia pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT botterodaniela pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT gaillardmariaemilia pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT castumacelina pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT rudierika pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT lodeiroanibal pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture
AT hozbordanielaf pertussisvaccinecandidatebasedonoutermembranevesiclesderivedfrombiofilmculture