Dual Antigen Display on an AP205 VLP Platform Elicits Potent and Durable Neutralization of EBV Infection in B Cells and Epithelial Cells In Vitro.

Authors

Xiaojuan Han, Ping Gao, Yuanyuan Shi, Chao Li, Xiaoyu Zhai, Guokai Feng, Musheng Zeng, Baidong Hou, Jian Song, Fuping Zhang

Published in

Vaccines. Volume 14. Issue 9. Aug 25, 2026. Epub Aug 25, 2026.

Abstract

Epstein-Barr virus (EBV) is a ubiquitous pathogen responsible for significant malignancies and autoimmune diseases, yet no prophylactic vaccine is available. The viral entry glycoproteins gL/gH and gB are essential for infection, but soluble forms are poorly immunogenic and fail to elicit durable neutralizing antibodies. Moreover, EBV infects both B cells and epithelial cells, demanding broad neutralization. This study aimed to develop a virus-like particle (VLP) platform that displays gL/gH and gB in a dense, repetitive array to overcome these barriers.
We conjugated recombinant gL/gH and gB to Acinetobacter phage AP205 VLPs using SpyTag/SpyCatcher covalent linkage, generating monovalent and bivalent chimeric nanoparticles (co-displaying both antigens on the same particle). Mice were immunized with these VLP constructs or alum-adjuvanted soluble proteins, and antibody responses, neutralization titres against B-cell and epithelial-cell infection, as well as germinal centre responses and durability, were assessed over a four-month period.
AP205-conjugated nanoparticles elicited significantly higher antigen-specific IgG titres than soluble proteins. The chimeric VLP, co-displaying gL/gH and gB, induced the stronger neutralising antibodies, effectively blocking EBV entry into both B cells and epithelial cells. Mechanistically, VLP immunization drove robust and sustained germinal centre reactions, resulting in increased plasma and memory B cells, and maintained neutralising activity for at least four months.
Precision nanoscale assembly of EBV entry glycoproteins on a synthetic VLP programs high-magnitude, broad-spectrum, and durable humoral immunity. The AP205-SpyTag platform offers a versatile and promising strategy for developing an effective prophylactic EBV vaccine.

PMID:
42797556
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.

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