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Infection and Immunity, April 2006, p. 2063-2071, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2063-2071.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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, and Bernard P. Arulanandam*

Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249

Received 10 November 2005/ Returned for modification 22 December 2005/ Accepted 11 January 2006

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 ({Delta}iglC) as a live attenuated vaccine against subsequent intranasal challenge with the wild-type organism. Animals primed with the F. novicida {Delta}iglC (KKF24) mutant induced robust splenic gamma interferon (IFN-{gamma}) 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-{gamma} 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.

* Corresponding author. Mailing address: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249. Phone: (210) 458-5492. Fax: (210) 458-5523. E-mail: barulanandam{at}utsa.edu.

Editor: J. T. Barbieri

Infection and Immunity, April 2006, p. 2063-2071, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2063-2071.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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