Development of Yersinia pestis F1 antigen-loaded liposome vaccine against plague using microneedles as a delivery system

Abstract

The F1 protein of Yersinia pestis is a major antigen for triggering immunity against plague in animals. It was currently used as a model antigen to establish a technology platform for highly efficient antibody induction. F1 antigen-loaded liposomes (F1-liposomes) were prepared using the patent formulation of the platform. The F1-liposome was further tested in vitro using phosphate-buffered saline (PBS) as solvent and its F1 protein content was determined by bicinchoninic acid (BCA) assay. The prepared F1-liposomes were administered into immunocompetent Balb/c mice using microneedles to have them immunized. The blood of these immunized mice was periodically taken out every 7 days for 45 days for the evaluation of the anti-F1 IgG titer using enzyme-linked immunosorbent assay (ELISA). Furthermore, to confirm the immune responses, the contents of interleukin-4 (IL-4), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were determined 35 days post immunization using the BIO-Plex pro assay. The mice administered with F1-liposome demonstrated the strongest immunity by the anti-F1 IgG antibody titer assay, the cytokine response test and the animal challenge test, compare with the controls (PBS and F1-Alugel). These results show that it is possible to develop an effective F1-liposomes plague vaccine using microneedles as a delivery tool.