Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10964475 | Vaccine | 2014 | 7 Pages |
Abstract
Oral vaccination with the defined live attenuated Francisella novicida vaccine strain U112ÎiglB has been demonstrated to induce protective immunity against pulmonary challenge with the highly human virulent Francisella tularensis strain SCHU S4. However, this vaccination regimen requires a booster dose in mice and Exhibits 50% protective efficacy in the Fischer 344 rat model. To enhance the efficacy of this vaccine strain, we engineered U112ÎiglB to express the Salmonella typhimurium FljB flagellin D1 domain, a TLR5 agonist. The U112ÎiglB::fljB strain was highly attenuated for intracellular macrophage replication, and although the FljB protein was expressed within the cytosol, it exhibited TLR5 activation in a TLR5-expressing HEK cell line. Additionally, infection of splenocytes and lymphocytes with U112ÎiglB::fljB induced significantly greater TNF-α production than infection with U112ÎiglB. Oral vaccination with U112ÎiglB::fljB also induced significantly greater protection than U112ÎiglB against pulmonary SCHU S4 challenge in rats. The enhanced protection was accompanied by higher IgG2a production and serum-mediated reduction of Francisella infectivity. Thus, the U112ÎiglB::fljB strain may serve as a potential vaccine candidate against pneumonic tularemia.
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Authors
Aimee L. Cunningham, Kim Minh Dang, Jieh-Juen Yu, M. Neal Guentzel, Hans W. Heidner, Karl E. Klose, Bernard P. Arulanandam,