| Autor: |
Mlynek, Kevin D., Cline, Curtis R., Biryukov, Sergei S., Toothman, Ronald G., Bachert, Beth A., Klimko, Christopher P., Shoe, Jennifer L., Hunter, Melissa, Hedrick, Zander M., Dankmeyer, Jennifer L., Mou, Sherry, Fetterer, David P., Qiu, Ju, Lee, Eric D., Cote, Christopher K., Jia, Qingmei, Horwitz, Marcus A., Bozue, Joel A. |
| Zdroj: |
Human Vaccines & Immunotherapeutics; December 2023, Vol. 19 Issue: 3 |
| Abstrakt: |
ABSTRACTFrancisella tularensisis 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. tularensisstrains, we assembled and characterized a panel of F. tularensisisolates 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 capBgene 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 107CFU rLVS provided 100% protection against both Type A strains. Against the Type B strain, two doses of 107CFU rLVS provided 100% protection, and a single dose of 107CFU provided 87.5% protection. In contrast, all unvaccinated rats succumbed to aerosol challenge with all of the F. tularensisstrains. A robust Th1-biased antibody response was induced in all vaccinated rats against all F. tularensisstrains. These results demonstrate that rLVS ΔcapB/iglABCprovides potent protection against inhalational challenge with either Type A or Type B F. tularensisstrains and should be considered for further analysis as a future tularemia vaccine. |
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