A VZV-gE subunit vaccine decorated with mPLA elicits protective cellular immmune responses against varicella-zoster virus

Herpes zoster is an acute infectious skin disease caused by the reactivation of latent varicella-zoster virus, vaccination, such as subunit vaccine with good safety, can effectively prevent shingles through increasing immunity of the body. However, protein antigens are prone to degradation and inactivation, which alone is generally not sufficient to induce potent immune effect. In this study, the liposomal vaccine platform modified with mPLA (TLR4 agonist) was developed to improve the immunogenicity of glycoprotein E (VZV-gE) derived from herpes zoster virus. The thin-film dispersion and freeze-drying methods were employed to encapsulate VZV-gE against degradation, enhance liposomal stability, and achieve better redissolution effects with an optimized cryoprotectant. The in vitro results presented that mPLA could effectively enhance the uptake of VZV-gE with DC2.4. In vivo immune effect evaluation showed that the prepared subunit vaccines could induce stronger IgG, IgG1, and IgG2a antibody levels in the mouse serum, improving humoral immune effects. And the secretion levels of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4, IL-10) in the splenocytes were significantly increased, inducing protective cellular immune responses. Overall, this work presented that combining immunomodulatory adjuvants decorated nanocarriers to develop subunit vaccine platforms was a promising strategy to prevent the occurrence of herpes zoster effectively.