Novel vaccination strategy: Francisella tularensis vaccines based on functionalized catanionic vesicles (VAC7P.963)

Abstract

Francisella tularensis (Ft) is a Gram-negative, immune-evasive coccobacillus that causes tularemia for which there is no FDA-approved vaccine. We have utilized a novel vaccine approach using synthetic nanoparticles made from catanionic surfactant vesicles (V), functionalized by incorporation of either Ft type B Live Vaccine Strain (Ft LVS) or Ft type A Schu S4 strain (Ft Schu S4) components (i.e., LVS-V and Schu S4-V, respectively). Immunization of C57BL/6 mice with bare V partially protected against Ft LVS, presumably through activation of an innate immune response, yet failed to protect against Ft Schu S4. In contrast, immunization with LVS-V fully protected mice against intraperitoneal (i.p.) Ft LVS challenge, while immunization of mice with either LVS-V or Schu S4-V partially protected C57BL/6 mice against an intranasal (i.n.) Ft Schu S4 challenge. LVS-V-immunization, but not immunization with V, elicited high levels of IgG against non-LPS epitopes and these antisera conferred passive protection against challenge with Ft LVS. Our recently published and ongoing studies aim to identify the protein targets of mouse antisera, study the mechanism of non-specific protection gained by immunization with this nanoparticle vaccine platform (adjuvant effect) in Ft LVS challenge, and enhance protection in Ft Schu S4 challenge. Our data extend the utility of functionalized catanionic surfactant vesicles as a vaccine platform for pathogens.