Polymer Nanosphere-Based Vaccination Strategies against Yersinia Pestis

Yersinia pestis, the causative agent of bubonic and pneumonic plague, is a Category A bioterrorism agent for which only moderately effective multi-dose whole-killed or live-attenuated vaccines currently exist. Subunit vaccines have been recently studied, but current strategies have shown only short-lived protection and require multiple injections. Our work is focused on the utilization of a fusion protein based (F1-V) vaccine, delivered with polyanhydride nanoparticle adjuvants as an inoculation strategy that will lead to a single-dose plague vaccine. For this study, random copolymers of 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane and 1,6-bis(p-carboxyphenoxy)hexane were synthesized and fabricated into F1-V loaded nanoparticles by anti-solvent precipitation. Nanoparticles were delivered intranasally to C57BL/6 mice. Antigen-specific immune responses were assessed by antibody titers using an ELISA and lymphocyte proliferation was evaluated with 3H-thymidine and carboxyfluorescein succinimidyl ester incorporation. Cytokine secretion was measured using a LUMINEX bead assay. The results show that polyanhydride nanoparticle adjuvants can enhance and modulate the immune response in a way that can potentially improve the effectiveness of the F1-V vaccine and allow for single dose delivery. These studies provide evidence that polyanhydride nanoparticle vehicles hold great potential to be used in a wide variety of vaccination strategies.