Vaccination with a defined Francisella tularensis subsp. novicida pathogenicity island mutant (ΔiglB) induces protective immunity against homotypic and heterotypic challenge

Yu Cong, Jieh Juen Yu, M. Neal Guentzel, Michael T. Berton, Janakiram Seshu, Karl E. Klose, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Francisella tularensis, an intracellular Gram-negative bacterium, is the causative agent of tularemia and a potential bioweapon. Currently, there is no licensed vaccine against this organism. We have characterized the efficacy of a defined F. tularensis subsp. novicida mutant (ΔiglB) as a live attenuated vaccine against pneumonic tularemia. Replication of the iglB mutant (KKF235) in murine macrophages was significantly lower than the wild type novicida strain U112, and exhibited an LD50 greater than 106-fold (>107 CFU vs <10 CFU) in an intranasal challenge model. Mice immunized with KKF235 intranasally or orally induced robust antigen-specific splenic IFN-γ recall responses, as well as the production of systemic and mucosal antibodies. Intranasal vaccination with KKF235 protected mice from subsequent homotypic challenge with U112 as well as heterotypic challenge with F. tularensis subsp. holarctica (LVS). Moreover, protected animals also exhibited minimal pathological changes compared with mock-vaccinated and challenged animals. The protection conferred by KKF235 vaccination was shown to be highly dependent on endogenous IFN-γ production. Most significantly, oral immunization with KKF235 protected mice from a highly lethal subsp. tularensis (SCHU S4) pulmonary challenge. Collectively, these results further suggest the feasibility of using defined pathogenicity island mutants as live vaccine candidates against pneumonic tularemia.

Original languageEnglish (US)
Pages (from-to)5554-5561
Number of pages8
JournalVaccine
Volume27
Issue number41
DOIs
StatePublished - Sep 18 2009

Keywords

  • Defined attenuated vaccines
  • Francisella tularensis
  • Mouse model
  • Oral vaccination
  • Pulmonary tularemia
  • Respiratory immunity

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 'Vaccination with a defined Francisella tularensis subsp. novicida pathogenicity island mutant (ΔiglB) induces protective immunity against homotypic and heterotypic challenge'. Together they form a unique fingerprint.

Cite this