Backgrounds: A contemporary public health challenge is the increase in the prevalence rates of herpes zoster (HZ) worldwide. Methods: In this work, the gE gene structure was analyzed using bioinformatics techniques, and three plasmids of varying lengths, tgE537, tgE200, and tgE350, were expressed in Chinese hamster ovary (CHO) cells. These proteins were used to immunize BALB/c mice with Al/CpG adjuvant; ELISPOT and FCM were used to evaluate cellular immunity; and ELISA, VZV microneutralization, and FAMA assays were performed to detect antibody titers. Results: Target protein concentrations of 1.8 mg/mL for tgE537, 0.15 mg/mL for tgE200 and 0.65 mg/mL for tgE350 were effectively produced. The ability of the three protein segments to stimulate CD4⁺ and CD8⁺ T cells, as well as to cause lymphocytes to secrete IFN-γ and IL-4, did not significantly differ from one another. Both tgE537 and tgE350 were capable of generating VZV-specific antibodies and neutralizing antibodies, while tgE350 had the highest neutralizing antibody titer (4388). There was no equivalent humoral immune response induced by tgE200. Conclusions: The results of this investigation provide the groundwork for the creation of HZ recombinant vaccines using truncated proteins as antigens.

Background: Herpes zoster (HZ), caused by the reactivation of varicella-zoster virus (VZV), primarily affects elderly populations worldwide. Although current recombinant HZ vaccines show strong immunogenicity, their high cost and potential side effects may limit their widespread use. Therefore, developing a cost-effective HZ vaccine with improved safety profiles would have significant clinical and public health implications. Methods: Building upon our previously optimized truncated gE (tgE350) from VZV, we developed the tgE350 + Fe nanoparticle vaccine using SpyTag/SpyCatcher covalent conjugation. The tgE350 protein (with a SpyTag tag) and the Fe protein (with a SpyCatcher tag) were expressed in HEK293F and E. coli BL21, respectively, enabling spontaneous nanoparticle assembly. Protein expression and nanoparticle formation were confirmed through SDS-PAGE and negative-stain electron microscopy. BALB/c mice were inoculated with either tgE350 + Fe or tgE350 combined with Al and CpG adjuvants. Immune responses were evaluated using ELISpot and flow cytometry for cellular immunity, along with ELISA, VZV microneutralization, and fluorescent antibody membrane antigen (FAMA) assays for antibody titers. Histopathological examination of major organs ensured vaccine safety. Results: Compared with the truncated vaccine tgE350, the nanoparticle vaccine tgE350 + Fe significantly enhanced VZV neutralizing antibodies and specific antibody responses in mice without causing significant changes in lymphocyte populations (no difference from the control group). Moreover, the tgE350 + Fe group had significantly more lymphocytes secreting IFN-γ, IL-2, and IL-4 than the tgE350 group. No apparent pathological damage was observed in the heart, liver, spleen, or lungs of mice in any experimental group. Conclusions: This experiment successfully developed the HZ nanoparticle vaccine tgE350 + Fe. It enhanced VZV-specific neutralizing antibodies, generated better cellular and humoral immune responses, and demonstrated good safety.