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Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates

Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. n...

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Autores principales: Chu, Ping, Cunningham, Aimee L., Yu, Jieh-Juen, Nguyen, Jesse Q., Barker, Jeffrey R., Lyons, C. Rick, Wilder, Julie, Valderas, Michelle, Sherwood, Robert L., Arulanandam, Bernard P., Klose, Karl E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207810/
https://www.ncbi.nlm.nih.gov/pubmed/25340543
http://dx.doi.org/10.1371/journal.ppat.1004439
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author Chu, Ping
Cunningham, Aimee L.
Yu, Jieh-Juen
Nguyen, Jesse Q.
Barker, Jeffrey R.
Lyons, C. Rick
Wilder, Julie
Valderas, Michelle
Sherwood, Robert L.
Arulanandam, Bernard P.
Klose, Karl E.
author_facet Chu, Ping
Cunningham, Aimee L.
Yu, Jieh-Juen
Nguyen, Jesse Q.
Barker, Jeffrey R.
Lyons, C. Rick
Wilder, Julie
Valderas, Michelle
Sherwood, Robert L.
Arulanandam, Bernard P.
Klose, Karl E.
author_sort Chu, Ping
collection PubMed
description Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD) protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP). The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.
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spelling pubmed-42078102014-10-27 Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates Chu, Ping Cunningham, Aimee L. Yu, Jieh-Juen Nguyen, Jesse Q. Barker, Jeffrey R. Lyons, C. Rick Wilder, Julie Valderas, Michelle Sherwood, Robert L. Arulanandam, Bernard P. Klose, Karl E. PLoS Pathog Research Article Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD) protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP). The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform. Public Library of Science 2014-10-23 /pmc/articles/PMC4207810/ /pubmed/25340543 http://dx.doi.org/10.1371/journal.ppat.1004439 Text en © 2014 Chu 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
Chu, Ping
Cunningham, Aimee L.
Yu, Jieh-Juen
Nguyen, Jesse Q.
Barker, Jeffrey R.
Lyons, C. Rick
Wilder, Julie
Valderas, Michelle
Sherwood, Robert L.
Arulanandam, Bernard P.
Klose, Karl E.
Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates
title Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates
title_full Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates
title_fullStr Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates
title_full_unstemmed Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates
title_short Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates
title_sort live attenuated francisella novicida vaccine protects against francisella tularensis pulmonary challenge in rats and non-human primates
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207810/
https://www.ncbi.nlm.nih.gov/pubmed/25340543
http://dx.doi.org/10.1371/journal.ppat.1004439
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