The rLVS ΔcapB/iglABC vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent Francisella tularensis strains
Francisella tularensis is one of the several biothreat agents for which a licensed vaccine is needed. To ensure vaccine protection is achieved across a range of virulent F. tularensis strains, we assembled and characterized a panel of F. tularensis isolates to be utilized as challenge strains. A promising tularemia vaccine candidate is rLVS ΔcapB/iglABC (rLVS), in which the vector is the LVS strain with a deletion in the capB gene and which additionally expresses a fusion protein comprising immunodominant epitopes of proteins IglA, IglB, and IglC. Fischer rats were immunized subcutaneously 1-3 times at 3-week intervals with rLVS at various doses. The rats were exposed to a high dose of aerosolized Type A strain Schu S4 (FRAN244), a Type B strain (FRAN255), or a tick derived Type A strain (FRAN254) and monitored for survival. All rLVS vaccination regimens including a single dose of 107 CFU rLVS provided 100% protection against both Type A strains. Against the Type B strain, two doses of 107 CFU rLVS provided 100% protection, and a single dose of 107 CFU provided 87.5% protection. In contrast, all unvaccinated rats succumbed to aerosol challenge with all of the F. tularensis strains. A robust Th1-biased antibody response was induced in all vaccinated rats against all F. tularensis strains. These results demonstrate that rLVS ΔcapB/iglABC provides potent protection against inhalational challenge with either Type A or Type B F. tularensis strains and should be considered for further analysis as a future tularemia vaccine.
| Errataetall: |
ErratumIn: Hum Vaccin Immunother. 2024 Dec 31;20(1):2307699. - PMID 38282336 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Human vaccines & immunotherapeutics - 19(2023), 3 vom: 15. Dez., Seite 2277083 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mlynek, Kevin D [VerfasserIn] |
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| Links: |
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| Themen: |
Aerosol challenge |
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| Anmerkungen: |
Date Completed 20.11.2023 Date Revised 29.01.2024 published: Print-Electronic ErratumIn: Hum Vaccin Immunother. 2024 Dec 31;20(1):2307699. - PMID 38282336 Citation Status MEDLINE |
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| doi: |
10.1080/21645515.2023.2277083 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The rLVS ΔcapB/iglABC vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent Francisella tularensis strains |
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| 500 | |a ErratumIn: Hum Vaccin Immunother. 2024 Dec 31;20(1):2307699. - PMID 38282336 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Francisella tularensis is one of the several biothreat agents for which a licensed vaccine is needed. To ensure vaccine protection is achieved across a range of virulent F. tularensis strains, we assembled and characterized a panel of F. tularensis isolates to be utilized as challenge strains. A promising tularemia vaccine candidate is rLVS ΔcapB/iglABC (rLVS), in which the vector is the LVS strain with a deletion in the capB gene and which additionally expresses a fusion protein comprising immunodominant epitopes of proteins IglA, IglB, and IglC. Fischer rats were immunized subcutaneously 1-3 times at 3-week intervals with rLVS at various doses. The rats were exposed to a high dose of aerosolized Type A strain Schu S4 (FRAN244), a Type B strain (FRAN255), or a tick derived Type A strain (FRAN254) and monitored for survival. All rLVS vaccination regimens including a single dose of 107 CFU rLVS provided 100% protection against both Type A strains. Against the Type B strain, two doses of 107 CFU rLVS provided 100% protection, and a single dose of 107 CFU provided 87.5% protection. In contrast, all unvaccinated rats succumbed to aerosol challenge with all of the F. tularensis strains. A robust Th1-biased antibody response was induced in all vaccinated rats against all F. tularensis strains. These results demonstrate that rLVS ΔcapB/iglABC provides potent protection against inhalational challenge with either Type A or Type B F. tularensis strains and should be considered for further analysis as a future tularemia vaccine | ||
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| 700 | 1 | |a Biryukov, Sergei S |e verfasserin |4 aut | |
| 700 | 1 | |a Toothman, Ronald G |e verfasserin |4 aut | |
| 700 | 1 | |a Bachert, Beth A |e verfasserin |4 aut | |
| 700 | 1 | |a Klimko, Christopher P |e verfasserin |4 aut | |
| 700 | 1 | |a Shoe, Jennifer L |e verfasserin |4 aut | |
| 700 | 1 | |a Hunter, Melissa |e verfasserin |4 aut | |
| 700 | 1 | |a Hedrick, Zander M |e verfasserin |4 aut | |
| 700 | 1 | |a Dankmeyer, Jennifer L |e verfasserin |4 aut | |
| 700 | 1 | |a Mou, Sherry |e verfasserin |4 aut | |
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| 700 | 1 | |a Qiu, Ju |e verfasserin |4 aut | |
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| 700 | 1 | |a Bozue, Joel A |e verfasserin |4 aut | |
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