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Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Construction and Immunological Evaluation of a Bicomponent Zika mRNA Vaccine
Qi Su1,2, Tingyi Che1,2, Shuai Shang1,2
1Changchun Bioproducts Research Co., Ltd., Changchun 130103, China.
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.

