Co‐Delivery of Varicella Zoster Virus gE and gI Dual‐Antigen mRNA Vaccine With CpG‐ODN Elicits Robust Immunity
- 1State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, School of Life Sciences, Xiamen University
Abstract
Herpes zoster (HZ), caused by reactivation of latent varicella zoster virus (VZV), remains a growing health burden. Developing new HZ vaccines with high efficacy and improved tolerability could address limitations of current vaccines and increase vaccination uptake and completion rates. To identify an optimal antigen design, we systematically evaluated multiple mRNA candidates based on VZV glycoprotein E (gE) and I (gI). In mice, membrane‐localized gE induced the strongest and most durable antibody responses, whereas inclusion of gI markedly enhanced T‐cell responses. Co‐delivery of membrane‐localized gE and gI (gE+gI Lmix) elicited the most robust cellular responses, outperforming both single‐antigen and fusion constructs. We therefore selected gE+gI Lmix for further optimization with CpG oligodeoxynucleotide (CpG‐ODN) adjuvants. In both naïve and VZV‐primed mice, CpG‐ODN 1018 increased neutralizing antibody titers and significantly enhanced antigen‐specific CD4+ and CD8+ IFN‐γ+ T‐cell responses, with a Th1‐biased profile. The resulting humoral and cellular responses matched or exceeded those induced by Shingrix in mice. Safety assessments revealed no distinct systemic toxicity or histopathological abnormalities following CpG‐ODN 1018 administration. Together, these findings identify dual‐antigen gE/gI mRNA vaccination, particularly in combination with CpG‐ODN 1018, as a promising strategy for HZ prevention, with enhanced cellular immunogenicity and an acceptable preclinical safety profile.
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BibTeX
@article{cui2026codelivery,
title = {{Co‐Delivery of Varicella Zoster Virus gE and gI Dual‐Antigen mRNA Vaccine With CpG‐ODN Elicits Robust Immunity}},
author = {Lingyan Cui and Sibo Zhang and Wenhui Xue and Hongjing Liu and Hong Wang and Hai Li and Yarong Zeng and Huizheng Zhang and Yaohan Li and Minqing Hong and Lin Chen and Jun Zhang and Ying Gu and Shaowei Li and Tingting Li and Ningshao Xia},
journal = {MedComm},
year = {2026},
month = nov,
doi = {10.1002/mco2.71117},
url = {https://europepmc.org/article/PMC/PMC13725205},
note = {CC BY},
}
RIS
TY - JOUR
TI - Co‐Delivery of Varicella Zoster Virus gE and gI Dual‐Antigen mRNA Vaccine With CpG‐ODN Elicits Robust Immunity
AU - Lingyan Cui
AU - Sibo Zhang
AU - Wenhui Xue
AU - Hongjing Liu
AU - Hong Wang
AU - Hai Li
AU - Yarong Zeng
AU - Huizheng Zhang
AU - Yaohan Li
AU - Minqing Hong
AU - Lin Chen
AU - Jun Zhang
AU - Ying Gu
AU - Shaowei Li
AU - Tingting Li
AU - Ningshao Xia
PY - 2026
DA - 2026/11/01
JO - MedComm
DO - 10.1002/mco2.71117
UR - https://europepmc.org/article/PMC/PMC13725205
AB - Herpes zoster (HZ), caused by reactivation of latent varicella zoster virus (VZV), remains a growing health burden. Developing new HZ vaccines with high efficacy and improved tolerability could address limitations of current vaccines and increase vaccination uptake and completion rates. To identify an optimal antigen design, we systematically evaluated multiple mRNA candidates based on VZV glycoprotein E (gE) and I (gI). In mice, membrane‐localized gE induced the strongest and most durable antibody responses, whereas inclusion of gI markedly enhanced T‐cell responses. Co‐delivery of membrane‐localized gE and gI (gE+gI Lmix) elicited the most robust cellular responses, outperforming both single‐antigen and fusion constructs. We therefore selected gE+gI Lmix for further optimization with CpG oligodeoxynucleotide (CpG‐ODN) adjuvants. In both naïve and VZV‐primed mice, CpG‐ODN 1018 increased neutralizing antibody titers and significantly enhanced antigen‐specific CD4+ and CD8+ IFN‐γ+ T‐cell responses, with a Th1‐biased profile. The resulting humoral and cellular responses matched or exceeded those induced by Shingrix in mice. Safety assessments revealed no distinct systemic toxicity or histopathological abnormalities following CpG‐ODN 1018 administration. Together, these findings identify dual‐antigen gE/gI mRNA vaccination, particularly in combination with CpG‐ODN 1018, as a promising strategy for HZ prevention, with enhanced cellular immunogenicity and an acceptable preclinical safety profile.
SN - 2688-2663
ER -