Intranasal vaccination with a defined attenuated Francisella novicida strain induces gamma interferon-dependent antibody-mediated protection against tularemia

Michael A. Pammit, Erin K. Raulie, Crystal M. Lauriano, Karl E. Klose, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Francisella tularensis is an intracellular gram-negative bacterium that is the causative agent of tularemia and a potential bioweapon. We have characterized the efficacy of a defined F. novicida mutant (ΔiglC) as a live attenuated vaccine against subsequent intranasal challenge with the wild-type organism. Animals primed with the F. novicida ΔiglC (KKF24) mutant induced robust splenic gamma interferon (IFN-γ) and interleukin-12 (IL-12) recall responses with negligible IL-4 production as well as the production of antigen-specific serum immunoglobulin G1 (IgG1) and IgG2a antibodies. BALB/c mice vaccinated intranasally (i.n.) with KKF24 and subsequently challenged with wild-type F. novicida (100 and 1,000 50% lethal doses) were highly protected (83% and 50% survival, respectively) from the lethal challenges. The protection conferred by KKF24 vaccination was shown to be highly dependent on endogenous IFN-γ production and also was mediated by antibodies that could be adoptively transferred to naive B-cell-deficient mice by inoculation of immune sera. Collectively, the results demonstrate that i.n. vaccination with KKF24 induces a vigorous Th1-type cytokine and antibody response that is protective against subsequent i.n. challenge with the wild-type strain. This is the first report of a defined live attenuated strain providing protection against the inhalation of F. novicida.

Original languageEnglish (US)
Pages (from-to)2063-2071
Number of pages9
JournalInfection and immunity
Volume74
Issue number4
DOIs
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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