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Infection and Immunity, May 2005, p. 2644-2654, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2644-2654.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Intranasal Vaccination Induces Protective Immunity against Intranasal Infection with Virulent Francisella tularensis Biovar A

Terry H. Wu,1 Julie A. Hutt,1,2 Kristin A. Garrison,1 Lyudmila S. Berliba,1 Yan Zhou,3 and C. Rick Lyons1*

Immunology, Inflammation and Infectious Disease Center, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, New Mexico,1 Lovelace Respiratory Research Institute, Albuquerque, New Mexico,2 Centers for Disease Control and Prevention, Fort Collins, Colorado3

Received 1 June 2004/ Returned for modification 14 August 2004/ Accepted 27 December 2004

The inhalation of Francisella tularensis biovar A causes pneumonic tularemia associated with high morbidity and mortality rates in humans. Exposure to F. tularensis usually occurs by accident, but there is increasing awareness that F. tularensis may be deliberately released in an act of bioterrorism or war. The development of a vaccine against pneumonic tularemia has been limited by a lack of information regarding the mechanisms required to protect against this disease. Vaccine models for F. tularensis in inbred mice would facilitate investigations of the protective mechanisms and significantly enhance vaccine development. Intranasal vaccination with the attenuated live vaccine strain (LVS) of F. tularensis reproducibly protected BALB/c mice, but not C57BL/6 mice, against intranasal and subcutaneous challenges with a virulent clinical isolate of F. tularensis biovar A (NMFTA1). The resistance of LVS-vaccinated BALB/c mice to intranasal NMFTA1 challenge was increased 100-fold by boosting with live NMFTA1 but not with LVS. The protective response was specific for F. tularensis and required both CD4 and CD8 T cells. The vaccinated mice appeared outwardly healthy for more than 2 months after NMFTA1 challenge, even though NMFTA1 was recovered from more than half of the vaccinated mice. These results show that intranasal vaccination induces immunity that protects BALB/c mice from intranasal infection by F. tularensis biovar A.

* Corresponding author. Mailing address: Department of Internal Medicine, University of New Mexico, 1 University of New Mexico, MSC10 5550, Albuquerque, NM 87131. Phone: (505) 272-4450. Fax: (505) 272-9912. E-mail: clyons{at}salud.unm.edu.

Editor: J. D. Clements

Infection and Immunity, May 2005, p. 2644-2654, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2644-2654.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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