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While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher\/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB\/c and C57BL\/6 mice\u2014responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE\/XUA01 generated IFN-\u03b3 and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines.<\/jats:p>","DOI":"10.3390\/ijms25189872","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T10:15:27Z","timestamp":1726136127000},"page":"9872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Glycoprotein E-Displaying Nanoparticles Induce Robust Neutralizing Antibodies and T-Cell Response against Varicella Zoster Virus"],"prefix":"10.3390","volume":"25","author":[{"given":"Hong","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, School of Life Sciences, Xiamen University, Xiamen 361102, China"},{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine 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