Poly-γ-Glutamic Acid Nanoparticles and Aluminum Adjuvant Used as an Adjuvant with a Single Dose of Japanese Encephalitis Virus-Like Particles Provide Effective Protection from Japanese Encephalitis Virus

To maintain immunity against Japanese encephalitis virus (JEV), a formalin-inactivated Japanese encephalitis (JE) vaccine should be administered several times. The repeated vaccination is not helpful in the case of a sudden outbreak of JEV or when urgent travel to a high-JEV-risk region is required; however, there are few single-injection JE vaccine options. In the present study, we investigated the efficacy of a single dose of a new effective JE virus-like particle preparation containing the JE envelope protein (JE-VLP). Although single administration with JE-VLP protected less than 50% of mice against lethal JEV infection, adding poly(gamma-glutamic acid) nanoparticles (gamma-PGA-NPs) or aluminum adjuvant (alum) to JE-VLP significantly protected more than 90% of the mice. A single injection of JE-VLP with either gamma-PGA-NPs or alum induced a significantly greater anti-JEV neutralizing antibody titer than JE-VLP alone. The enhanced titers were maintained for more than 6 months, resulting in long-lasting protection of 90% of the immunized mice. Although the vaccine design needs further modification to reach 100% protection, a single dose of JE-VLP with gamma-PGA-NPs may be a useful step in developing a next-generation vaccine to stop a JE outbreak or to immunize travelers or military personnel.