The rLVS ΔcapB/iglABC vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent Francisella tularensis strains

• Published in: Human vaccines & immunotherapeutics Vol. 19; no. 3; p. 2277083
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 15.12.2023; Taylor & Francis Group
• Subjects: aerosol challenge; animal model; Animals; Bacterial Vaccines; Disease Models, Animal; Francisella tularensis; Francisella tularensis - genetics; LVS (Live Vaccine Strain); Mice; Mice, Inbred BALB C; Novel Vaccines; rat; Rats; Rats, Inbred F344; tularemia; Tularemia - prevention & control; vaccines; Vaccines, Attenuated; aerosol challenge; LVS (Live Vaccine Strain); rat; tularemia; vaccines; animal model; Francisella tularensis
• ISSN: 2164-5515; 2164-554X
• DOI: 10.1080/21645515.2023.2277083

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 10 7 CFU rLVS provided 100% protection against both Type A strains. Against the Type B strain, two doses of 10 7 CFU rLVS provided 100% protection, and a single dose of 10 7 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.