title: Novel catanionic surfactant vesicle vaccines protect against Francisella tularensis LVS and confer significant partial protection against F. tularensis Schu S4 strain.
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.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA.
authors.forename: Katharina
authors.initials: K
authors.lastname: Richard
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Mann
authors.forename: Lenea
authors.initials: L
authors.lastname: Stocker
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Barry
authors.forename: Aiping
authors.initials: A
authors.lastname: Qin
authors.forename: Leah E
authors.initials: LE
authors.lastname: Cole
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Hurley
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Michalek
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Stein
authors.forename: Philip
authors.initials: P
authors.lastname: Deshong
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Vogel
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D005604:Francisella tularensis / Q000276:immunology*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D014406:Tularemia / Q000517:prevention & control*; D053835:Unilamellar Liposomes / Q000008:administration & dosage*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004337:Drug Carriers; D007074:Immunoglobulin G; D053835:Unilamellar Liposomes; D014613:Vaccines, Attenuated