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VACCINE RESEARCH

Intranasal Administration of an Inactivated Yersinia pestis Vaccine with Interleukin-12 Generates Protective Immunity against Pneumonic Plague

Devender Kumar, Girish Kirimanjeswara, Dennis W. Metzger
Devender Kumar
Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208
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Girish Kirimanjeswara
Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208
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Dennis W. Metzger
Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208
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  • For correspondence: metzged@mail.amc.edu
DOI: 10.1128/CVI.05117-11
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ABSTRACT

Inhalation of Yersinia pestis causes pneumonic plague, which rapidly progresses to death. A previously licensed killed whole-cell vaccine is presently unavailable due to its reactogenicity and inconclusive evidence of efficacy. The present study now shows that vaccination intranasally (i.n.) with inactivated Y. pestis CO92 (iYp) adjuvanted with interleukin-12 (IL-12) followed by an i.n. challenge with a lethal dose of Y. pestis CO92 prevented bacterial colonization and protected 100% of mice from pneumonic plague. Survival of the vaccinated mice correlated with levels of systemic and lung antibodies, reduced pulmonary pathology and proinflammatory cytokines, and the presence of lung lymphoid cell aggregates. Protection against pneumonic plague was partially dependent upon Fc receptors and could be transferred to naïve mice with immune mouse serum. On the other hand, protection was not dependent upon complement, and following vaccination, depletion of CD4 and/or CD8 T cells before challenge did not affect survival. In summary, the results demonstrate the safety, immunogenicity, and protective efficacy of i.n. administered iYp plus IL-12 in a mouse model of pneumonic plague.

FOOTNOTES

    • Received 25 April 2011.
    • Returned for modification 13 May 2011.
    • Accepted 18 August 2011.
    • Accepted manuscript posted online 31 August 2011.
  • ↵# Supplemental material for this article may be found at http://dx.doi.org/10.1128/CVI.05117-11.

  • Copyright © 2011, American Society for Microbiology. All Rights Reserved.
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Intranasal Administration of an Inactivated Yersinia pestis Vaccine with Interleukin-12 Generates Protective Immunity against Pneumonic Plague
Devender Kumar, Girish Kirimanjeswara, Dennis W. Metzger
Clinical and Vaccine Immunology Nov 2011, 18 (11) 1925-1935; DOI: 10.1128/CVI.05117-11

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Intranasal Administration of an Inactivated Yersinia pestis Vaccine with Interleukin-12 Generates Protective Immunity against Pneumonic Plague
Devender Kumar, Girish Kirimanjeswara, Dennis W. Metzger
Clinical and Vaccine Immunology Nov 2011, 18 (11) 1925-1935; DOI: 10.1128/CVI.05117-11
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