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Microbial Immunity and Vaccines

Inactivated Francisella tularensis Live Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion

Shawn D. Baron, Rajendra Singh, Dennis W. Metzger
Shawn D. Baron
Center for Immunology & Microbial Disease, Albany Medical College, Albany, New York 12208
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Rajendra Singh
Center for Immunology & Microbial Disease, Albany Medical College, Albany, New York 12208
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Dennis W. Metzger
Center for Immunology & Microbial Disease, Albany Medical College, Albany, New York 12208
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  • For correspondence: metzged@mail.amc.edu
DOI: 10.1128/IAI.01606-06
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ABSTRACT

Francisella tularensis is a gram-negative intracellular bacterium that is considered to be a potential category A biological weapon due to its extreme virulence. Although vaccination with the attenuated live vaccine strain (LVS) of F. tularensis can protect against lethal challenge, use of inactivated or subunit forms as vaccine candidates for induction of protective antibody responses has not been fully evaluated. In the present study, we examined whether immune protection in the lung could be stimulated by intranasal administration of inactivated LVS together with interleukin-12 (IL-12) as an adjuvant. LVS was inactivated by heat, paraformaldehyde treatment, or exposure to UV, and inactivation of the preparations was confirmed by assessing bacterial growth and the survival of mice after direct inoculation. We found that mucosal vaccination with inactivated LVS provided 90 to 100% protection in mice after lethal intranasal challenge with 104 CFU of LVS, and this protection was dependent on inclusion of exogenous IL-12 during vaccine administration. Survival of vaccinated mice after live bacterial challenge was correlated with reduced bacterial burden, decreased pulmonary inflammation, increased serum antibody titers, and lower levels of gamma interferon (IFN-γ), tumor necrosis factor alpha, and IL-6 in the lungs, livers, and spleens. Whereas NK cells were primarily responsible for the production of IFN-γ in unvaccinated, challenged animals, vaccinated mice had increased levels of lung IFN-γ+ CD4+ T cells after challenge. Significantly, mice genetically deficient in immunoglobulin A (IgA) expression were unable to survive lethal challenge after vaccination. These results are the first results to demonstrate that IgA-mediated protection against lethal respiratory tularemia occurs after mucosal vaccination with inactivated F. tularensis LVS.

  • Copyright © 2007 American Society for Microbiology
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Inactivated Francisella tularensis Live Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion
Shawn D. Baron, Rajendra Singh, Dennis W. Metzger
Infection and Immunity Apr 2007, 75 (5) 2152-2162; DOI: 10.1128/IAI.01606-06

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Inactivated Francisella tularensis Live Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion
Shawn D. Baron, Rajendra Singh, Dennis W. Metzger
Infection and Immunity Apr 2007, 75 (5) 2152-2162; DOI: 10.1128/IAI.01606-06
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KEYWORDS

Bacterial Vaccines
Francisella tularensis
Immunoglobulin A
respiratory tract infections
tularemia
Vaccines, Inactivated

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