Enhancement of vaccine efficacy by expression of a TLR5 ligand in the defined live attenuated Francisella tularensis subsp. Novicida strain U112δiglB :: FljB

Aimee L. Cunningham, Kim Minh Dang, Jieh Juen Yu, M. Neal Guentzel, Hans W. Heidner, Karl E. Klose, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Oral vaccination with the defined live attenuated Francisella novicida vaccine strain U112δiglB 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 U112δiglB to express the Salmonella typhimurium FljB flagellin D1 domain, a TLR5 agonist. The U112δiglB::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 U112δiglB::fljB induced significantly greater TNF-α production than infection with U112δiglB. Oral vaccination with U112δiglB::fljB also induced significantly greater protection than U112δiglB 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 U112δiglB::fljB strain may serve as a potential vaccine candidate against pneumonic tularemia.

Original languageEnglish (US)
Pages (from-to)5234-5240
Number of pages7
JournalVaccine
Volume32
Issue number40
DOIs
StatePublished - Sep 8 2014

Keywords

  • Fischer 344 rat
  • Flagellin
  • Francisella tularensis
  • TLR5
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Enhancement of vaccine efficacy by expression of a TLR5 ligand in the defined live attenuated Francisella tularensis subsp. Novicida strain U112δiglB :: FljB'. Together they form a unique fingerprint.

Cite this