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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-10-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4207810?pdf=render |
| _version_ | 1818496866784903168 |
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| author | Ping Chu Aimee L Cunningham Jieh-Juen Yu Jesse Q Nguyen Jeffrey R Barker C Rick Lyons Julie Wilder Michelle Valderas Robert L Sherwood Bernard P Arulanandam Karl E Klose |
| author_facet | Ping Chu Aimee L Cunningham Jieh-Juen Yu Jesse Q Nguyen Jeffrey R Barker C Rick Lyons Julie Wilder Michelle Valderas Robert L Sherwood Bernard P Arulanandam Karl E Klose |
| author_sort | Ping Chu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T18:37:59Z |
| format | Article |
| id | doaj.art-1ebc0856ec494ab0b302746fca14d45d |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-10T18:37:59Z |
| publishDate | 2014-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-1ebc0856ec494ab0b302746fca14d45d2022-12-22T01:37:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-10-011010e100443910.1371/journal.ppat.1004439Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.Ping ChuAimee L CunninghamJieh-Juen YuJesse Q NguyenJeffrey R BarkerC Rick LyonsJulie WilderMichelle ValderasRobert L SherwoodBernard P ArulanandamKarl E KloseFrancisella 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.http://europepmc.org/articles/PMC4207810?pdf=render |
| spellingShingle | Ping Chu Aimee L Cunningham Jieh-Juen Yu Jesse Q Nguyen Jeffrey R Barker C Rick Lyons Julie Wilder Michelle Valderas Robert L Sherwood Bernard P Arulanandam Karl E Klose Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates. PLoS Pathogens |
| 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 |
| url | http://europepmc.org/articles/PMC4207810?pdf=render |
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