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Vaccines

Novel Catanionic Surfactant Vesicle Vaccines Protect against Francisella tularensis LVS and Confer Significant Partial Protection against F. tularensis Schu S4 Strain

Katharina Richard, Barbara J. Mann, Lenea Stocker, Eileen M. Barry, Aiping Qin, Leah E. Cole, Matthew T. Hurley, Robert K. Ernst, Suzanne M. Michalek, Daniel C. Stein, Philip DeShong, Stefanie N. Vogel
D. L. Burns, Editor
Katharina Richard
aDepartment of Microbiology and Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA
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Barbara J. Mann
bDepartment of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
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Lenea Stocker
cDepartment of Chemistry and Biochemistry, University of Maryland College Park, College Park, Maryland, USA
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Eileen M. Barry
dCenter for Vaccine Development, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA
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Aiping Qin
bDepartment of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
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Leah E. Cole
aDepartment of Microbiology and Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA
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Matthew T. Hurley
cDepartment of Chemistry and Biochemistry, University of Maryland College Park, College Park, Maryland, USA
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Robert K. Ernst
eDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland Baltimore, Baltimore, Maryland, USA
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Suzanne M. Michalek
fDepartment of Microbiology, University of Alabama Birmingham, Birmingham, Alabama, USA
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Daniel C. Stein
gDepartment of Cell Biology and Molecular Genetics, University of Maryland College Park, College Park, Maryland, USA
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Philip DeShong
cDepartment of Chemistry and Biochemistry, University of Maryland College Park, College Park, Maryland, USA
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Stefanie N. Vogel
aDepartment of Microbiology and Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA
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D. L. Burns
Roles: Editor
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DOI: 10.1128/CVI.00738-13
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ABSTRACT

Francisella tularensis is a Gram-negative immune-evasive coccobacillus that causes tularemia in humans and animals. A safe and efficacious vaccine that is protective against multiple F. tularensis strains has yet to be developed. In this study, we tested a novel vaccine approach using artificial pathogens, synthetic nanoparticles made from catanionic surfactant vesicles that are functionalized by the incorporation of either F. tularensis type B live vaccine strain (F. tularensis LVS [LVS-V]) or F. tularensis type A Schu S4 strain (F. tularensis Schu S4 [Schu S4-V]) components. The immunization of C57BL/6 mice with “bare” vesicles, which did not express F. tularensis components, partially protected against F. tularensis LVS, presumably through activation of the innate immune response, and yet it failed to protect against the F. tularensis Schu S4 strain. In contrast, immunization with LVS-V fully protected mice against intraperitoneal (i.p.) F. tularensis LVS challenge, while immunization of mice with either LVS-V or Schu S4-V partially protected C57BL/6 mice against an intranasal (i.n.) F. tularensis Schu S4 challenge and significantly increased the mean time to death for nonsurvivors, particularly following the i.n. and heterologous (i.e., i.p./i.n.) routes of immunization. LVS-V immunization, but not immunization with empty vesicles, elicited high levels of IgG against nonlipopolysaccharide (non-LPS) epitopes that were increased after F. tularensis LVS challenge and significantly increased early cytokine production. Antisera from LVS-V-immunized mice conferred passive protection against challenge with F. tularensis LVS. Together, these data indicate that functionalized catanionic surfactant vesicles represent an important and novel tool for the development of a safe and effective F. tularensis subunit vaccine and may be applicable for use with other pathogens.

FOOTNOTES

    • Received 19 November 2013.
    • Returned for modification 29 November 2013.
    • Accepted 6 December 2013.
    • Accepted manuscript posted online 18 December 2013.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/CVI.00738-13.

  • Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Novel Catanionic Surfactant Vesicle Vaccines Protect against Francisella tularensis LVS and Confer Significant Partial Protection against F. tularensis Schu S4 Strain
Katharina Richard, Barbara J. Mann, Lenea Stocker, Eileen M. Barry, Aiping Qin, Leah E. Cole, Matthew T. Hurley, Robert K. Ernst, Suzanne M. Michalek, Daniel C. Stein, Philip DeShong, Stefanie N. Vogel
Clinical and Vaccine Immunology Jan 2014, 21 (2) 212-226; DOI: 10.1128/CVI.00738-13

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Novel Catanionic Surfactant Vesicle Vaccines Protect against Francisella tularensis LVS and Confer Significant Partial Protection against F. tularensis Schu S4 Strain
Katharina Richard, Barbara J. Mann, Lenea Stocker, Eileen M. Barry, Aiping Qin, Leah E. Cole, Matthew T. Hurley, Robert K. Ernst, Suzanne M. Michalek, Daniel C. Stein, Philip DeShong, Stefanie N. Vogel
Clinical and Vaccine Immunology Jan 2014, 21 (2) 212-226; DOI: 10.1128/CVI.00738-13
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