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

TL;DR

Researchers developed a new nanoparticle-based vaccine for shingles that improves immune responses compared to the current standard vaccine.

Contribution

A novel modular nanoparticle platform using a licensed hepatitis E vaccine scaffold to display VZV gE for shingles vaccine development.

Findings

Nano-gEVZV showed enhanced antigen uptake by antigen-presenting cells and improved lymph node retention in mice.

The nano-vaccine elicited stronger B- and T-cell responses compared to Shingrix in mouse models.

Nanoparticle presentation synergized with adjuvants to enhance adaptive immunity against VZV gE.

Abstract

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.

Shingles, caused by reactivation of the VZV, remains a major health concern in older adults, for whom vaccination is the most effective preventive measure. In this study, we designed a nanoparticle-based gE vaccine (Nano-gEVZV) using a hepatitis E vaccine–derived platform to explore strategies for enhancing shingles vaccine immunogenicity. The Nano-gEVZV formulation, combined with an AS01B-like adjuvant, promoted efficient lymph node localization and enhanced antigen uptake by dendritic cells. In mouse models, Nano-gEVZV elicited stronger VZV gE-specific humoral and CD4 ⁺ T-cell responses compared with monomeric antigen formulations, highlighting how nanoparticle presentation can synergize with adjuvants to shape adaptive immunity. While these findings provide proof-of-concept evidence for the potential of modular nanoparticle display in herpes zoster vaccine development, further validation in human-relevant systems will be essential before clinical translation.

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