A modular nanoparticle display strategy for varicella-zoster virus gE based on a licensed protein scaffold.

Varicella-zoster virus (VZV), the cause of shingles, remains a significant health issue worldwide, particularly among aging populations. The recombinant zoster vaccine (Shingrix, RZV) is the only approved vaccine in many countries and has demonstrated >90% efficacy with durable protection lasting over a decade, highlighting the value of subunit vaccines targeting VZV glycoprotein E (VZV gE). Although RZV provides durable and highly effective protection, alternative vaccine platforms remain important for advancing antigen design and improving immune presentation. Advances in nanoparticle technology now enable antigens to be displayed in highly ordered, repetitive arrays, offering new opportunities to strengthen antiviral immunity. Here, we developed a novel nano-vaccine named Nano-gEVZV, which employs the antigen from the licensed Hepatitis E vaccine (Hecolin) as a nanoparticle scaffold and uses a nano-binder (NB) to display VZV gE in a repetitive arrangement. Nano-gEVZV demonstrates enhanced antigen uptake by antigen-presenting cells (APCs), improved lymph node retention, and stronger B- and T-cell responses compared with Shingrix in mouse models. While RZV remains the gold standard for herpes zoster prevention, we explored a nanoparticle-based gE display platform as a complementary approach to improve manufacturability and immune presentation.