Construction and Immunological Evaluation of a Bicomponent Zika mRNA Vaccine.
- 1Changchun Bioproducts Research Co., Ltd., Changchun 130103, China.
- 2National Institutes for Drug Control, Beijing 102629, China.
- 3SINOVAC BIOTECH CO., LTD., Beijing 102629, China.
Abstract
Background
There is evidence for the protective effects of antibodies targeting non-structural protein 1 (NS1) of Zika virus (ZIKV); however, effective vaccines against ZIKV remain lacking.Methods
In this study, lipid nanoparticle (LNP)-encapsulated mRNA vaccines were designed based on the envelope domain III (EDIII) and NS1 sequences of the ZIKV FSS13025 strain, while protective efficacy was evaluated in a murine model using a ZIKV isolate obtained from Zhejiang Provincial Center for Disease Control and Prevention (Zhejiang CDC).Results
The vaccines were evaluated for key quality attributes-including particle size, polydispersity index (PDI), and encapsulation efficiency-as well as immunogenicity and protective efficacy. Both monovalent vaccine components exhibited uniform particle sizes (PDI < 0.2) and high encapsulation efficiencies (≥80%) and induced high levels of antigen-specific antibodies in mice in a dose-dependent manner. The EDIII mRNA vaccine elicited moderate ZIKV-neutralizing antibody titers as measured by PRNT₅₀, whereas the NS1 vaccine did not induce detectable neutralizing antibodies. Both bicomponent (EDIII + NS1) mRNA vaccines induced a Th1-biased cellular immune response in mouse splenocytes, with significantly greater IFN-γ production compared with either monovalent vaccine. In viral challenge experiments using 1 × 10⁵ PFU ZIKV (Zhejiang CDC isolate, intraperitoneal), the bicomponent vaccine provided complete protection, with 100% survival across all dose groups. In contrast, the EDIII and NS1 monovalent vaccines showed partial protection: mortality was observed in the 20 μg dose groups and exceeded 50% in the 10 μg dose groups.Conclusions
These results demonstrate that the bicomponent EDIII + NS1 mRNA vaccine combination confers superior protective efficacy compared with either component alone, consistent with a synergistic effect between humoral and cellular immune responses. This study provides a novel strategy for next-generation Zika vaccine development.
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BibTeX
@article{su2026construction,
title = {{Construction and Immunological Evaluation of a Bicomponent Zika mRNA Vaccine.}},
author = {Qi Su and Tingyi Che and Shuai Shang and Xinzhu Wang and Xiaoqin Ge and Fang Cai and Hongyu Wang and Hongshan Xu and Qunying Mao and Xiaohong Wu and Xinyu Liu},
journal = {Vaccines},
year = {2026},
month = oct,
doi = {10.3390/vaccines14100897},
url = {https://europepmc.org/article/MED/42931426},
note = {CC BY},
}
RIS
TY - JOUR
TI - Construction and Immunological Evaluation of a Bicomponent Zika mRNA Vaccine.
AU - Qi Su
AU - Tingyi Che
AU - Shuai Shang
AU - Xinzhu Wang
AU - Xiaoqin Ge
AU - Fang Cai
AU - Hongyu Wang
AU - Hongshan Xu
AU - Qunying Mao
AU - Xiaohong Wu
AU - Xinyu Liu
PY - 2026
DA - 2026/10/13
JO - Vaccines
DO - 10.3390/vaccines14100897
UR - https://europepmc.org/article/MED/42931426
AB - Background There is evidence for the protective effects of antibodies targeting non-structural protein 1 (NS1) of Zika virus (ZIKV); however, effective vaccines against ZIKV remain lacking.Methods In this study, lipid nanoparticle (LNP)-encapsulated mRNA vaccines were designed based on the envelope domain III (EDIII) and NS1 sequences of the ZIKV FSS13025 strain, while protective efficacy was evaluated in a murine model using a ZIKV isolate obtained from Zhejiang Provincial Center for Disease Control and Prevention (Zhejiang CDC).Results The vaccines were evaluated for key quality attributes-including particle size, polydispersity index (PDI), and encapsulation efficiency-as well as immunogenicity and protective efficacy. Both monovalent vaccine components exhibited uniform particle sizes (PDI < 0.2) and high encapsulation efficiencies (≥80%) and induced high levels of antigen-specific antibodies in mice in a dose-dependent manner. The EDIII mRNA vaccine elicited moderate ZIKV-neutralizing antibody titers as measured by PRNT₅₀, whereas the NS1 vaccine did not induce detectable neutralizing antibodies. Both bicomponent (EDIII + NS1) mRNA vaccines induced a Th1-biased cellular immune response in mouse splenocytes, with significantly greater IFN-γ production compared with either monovalent vaccine. In viral challenge experiments using 1 × 10⁵ PFU ZIKV (Zhejiang CDC isolate, intraperitoneal), the bicomponent vaccine provided complete protection, with 100% survival across all dose groups. In contrast, the EDIII and NS1 monovalent vaccines showed partial protection: mortality was observed in the 20 μg dose groups and exceeded 50% in the 10 μg dose groups.Conclusions These results demonstrate that the bicomponent EDIII + NS1 mRNA vaccine combination confers superior protective efficacy compared with either component alone, consistent with a synergistic effect between humoral and cellular immune responses. This study provides a novel strategy for next-generation Zika vaccine development.
SN - 2076-393X
ER -