BC02-adjuvanted varicella-zoster virus glycoprotein E subunit vaccine overcomes immunosenescence to induce robust neutralizing antibodies and multifunctional T-cell immunity in seropositive aged murine models

After infection with the varicella-zoster virus (VZV), the virus becomes latent in the sensory ganglia. Immune senescence may lead to its reactivation, resulting in herpes zoster (HZ). The limited immunogenicity of current vaccines in elderly populations remains a significant challenge for prevention and control. This study investigated the immune-enhancing effects of the novel compound adjuvant BC02 on a recombinant VZV glycoprotein E (gE) subunit vaccine in a serum-positive elderly mouse model. A seropositive state was simulated through pre-immunization with the Oka strain of VZV, and the impacts of vaccines with various adjuvant formulations on humoral and cellular immunity in aged mice were systematically compared. Results demonstrated that the number of gE-specific IFN-γ- and IL-2-secreting cells induced by the BC02-adjuvanted vaccine (gE+BC02-1) increased 11.8- and 5.7-fold compared to the single-adjuvant group, significantly enhancing the multifunctionality of CD4+ T cells. The neutralizing antibody titer reached 1:122, comparable to that of the commercial vaccine Shingrix®, while the ratio of memory T/B cells was markedly higher than in the control group. Cross-age group experiments revealed that BC02 could overcome the limitations imposed by immune senescence in elderly models, inducing a balanced Th1/Th2 response and long-term immune memory comparable to that observed in younger groups (antibody titers maintained for ≥8 months). This study confirmed that the BC02 adjuvant synergistically activates innate and adaptive immunity, significantly enhancing the immune efficacy of the gE vaccine in serum-positive elderly individuals, thereby providing an potential strategy for optimizing herpes zoster vaccines for the elderly population.