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

被引:18
|
作者
Richard, Katharina [1 ]
Mann, Barbara J. [2 ]
Stocker, Lenea [3 ]
Barry, Eileen M. [4 ]
Qin, Aiping [2 ]
Cole, Leah E. [1 ]
Hurley, Matthew T. [3 ]
Ernst, Robert K. [5 ]
Michalek, Suzanne M. [6 ]
Stein, Daniel C. [7 ]
DeShong, Philip [3 ]
Vogel, Stefanie N. [1 ]
机构
[1] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
[2] Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA
[3] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA
[4] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA
[5] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA
[6] Univ Alabama, Dept Microbiol, Birmingham, MD USA
[7] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
SUBSPECIES TULARENSIS; INTRACELLULAR BACTERIUM; INTRANASAL VACCINATION; RESPIRATORY CHALLENGE; AEROSOL INFECTION; DELETION MUTANTS; IMMUNE-RESPONSE; O-ANTIGEN; MICE; TULAREMIA;
D O I
10.1128/CVI.00738-13
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:212 / 226
页数:15
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