A self-assembling ferritin nanoparticle-based trivalent vaccine of gB/gE/gH elicits potent immune responses against varicella-zoster virus.

The causes varicella and herpes zoster, posing a significant global health burden. ZOSTAVAX (live attenuated) and Shingrix (protein subunit) are the main vaccines against varicella-zoster virus (VZV). However, ZOSTAVAX was linked to three recent deaths in Australia, and AS01b-adjuvanted Shingrix often causes side effects like fever and inflammation. Therefore, developing a second recombinant VZV vaccine is highly significant. Here, we developed a trivalent VZV vaccine by displaying glycoproteins gB, gE, and gH on 24-mer ferritin nanoparticles, enhancing immunogenicity and broadening epitope coverage. Notably, the alum-adjuvanted trivalent vaccine avoided the use of AS01b, potentially reducing adverse reactions. In a head-to-head comparison with Shingrix, this trivalent vaccine elicited robust glycoprotein-specific IgG titers (≥106), high neutralizing antibody levels (FRNT₅₀ > 103), strong B cell responses, and comparable cytokine production by antigen-specific T cells (IFN-γ, IL-2, TNF-α). These findings demonstrate our trivalent nanoparticle vaccine offers a promising alternative to current VZV vaccines, combining broad antigen coverage with a potentially improved safety profile.