Abstract
Varicella-zoster virus (VZV) is a human neurotropic herpesvirus. The primary infection with VZV causes chickenpox and establishes latency in sensory and dorsal root ganglia. Viral reactivation leads to herpes zoster (HZ), which is accompanied by complications such as postherpetic neuralgia (PHN), causing a significant disease burden. At present, vaccination is the most effective preventive measure. We developed a recombinant zoster vaccine, gE/BFA01, which comprises truncated VZV glycoprotein E and the liposome-based adjuvant BFA01 (containing MPL and QS-21). In this study, we evaluated the recombinant zoster vaccine's immunogenicity in a live attenuated VZV-primed C57BL/6N mouse model and explored the mechanism of action of the BFA01 adjuvant. The results indicate that the gE/BFA01 vaccine induces superior antibody responses and stronger cellular immune responses compared with gE with aluminum hydroxide. Furthermore, gE/BFA01 showed comparable immunogenicity to the licensed vaccine Shingrix. Mechanistic investigations revealed that the BFA01 adjuvant can enhance the recruitment of innate immune cells at the injection site, increase the expression of DCs surface maturation markers, and activate multiple inflammatory signaling pathways in lymph nodes. Collectively, these findings indicate that gE/BFA01 can induce potent humoral and cellular responses, supporting its further development as a high-efficiency vaccine candidate.