Cargando…

Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination

BACKGROUND: No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer...

Descripción completa

Detalles Bibliográficos
Autores principales: Derbise, Anne, Hanada, Yuri, Khalifé, Manal, Carniel, Elisabeth, Demeure, Christian E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608741/
https://www.ncbi.nlm.nih.gov/pubmed/26473734
http://dx.doi.org/10.1371/journal.pntd.0004162
_version_ 1782395708985311232
author Derbise, Anne
Hanada, Yuri
Khalifé, Manal
Carniel, Elisabeth
Demeure, Christian E.
author_facet Derbise, Anne
Hanada, Yuri
Khalifé, Manal
Carniel, Elisabeth
Demeure, Christian E.
author_sort Derbise, Anne
collection PubMed
description BACKGROUND: No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. METHODOLOGY/PRINCIPAL FINDINGS: The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1—Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (10(8) CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD(50)) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD(50) Y. pestis and 93% against a high-dose infection (10,000 LD(50)). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1(-)) Y. pestis. SIGNIFICANCE: VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral administration.
format Online
Article
Text
id pubmed-4608741
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-46087412015-10-29 Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination Derbise, Anne Hanada, Yuri Khalifé, Manal Carniel, Elisabeth Demeure, Christian E. PLoS Negl Trop Dis Research Article BACKGROUND: No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. METHODOLOGY/PRINCIPAL FINDINGS: The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1—Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (10(8) CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD(50)) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD(50) Y. pestis and 93% against a high-dose infection (10,000 LD(50)). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1(-)) Y. pestis. SIGNIFICANCE: VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral administration. Public Library of Science 2015-10-16 /pmc/articles/PMC4608741/ /pubmed/26473734 http://dx.doi.org/10.1371/journal.pntd.0004162 Text en © 2015 Derbise et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Derbise, Anne
Hanada, Yuri
Khalifé, Manal
Carniel, Elisabeth
Demeure, Christian E.
Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination
title Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination
title_full Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination
title_fullStr Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination
title_full_unstemmed Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination
title_short Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination
title_sort complete protection against pneumonic and bubonic plague after a single oral vaccination
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608741/
https://www.ncbi.nlm.nih.gov/pubmed/26473734
http://dx.doi.org/10.1371/journal.pntd.0004162
work_keys_str_mv AT derbiseanne completeprotectionagainstpneumonicandbubonicplagueafterasingleoralvaccination
AT hanadayuri completeprotectionagainstpneumonicandbubonicplagueafterasingleoralvaccination
AT khalifemanal completeprotectionagainstpneumonicandbubonicplagueafterasingleoralvaccination
AT carnielelisabeth completeprotectionagainstpneumonicandbubonicplagueafterasingleoralvaccination
AT demeurechristiane completeprotectionagainstpneumonicandbubonicplagueafterasingleoralvaccination