A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice

Xinglong Liu, Zhengfeng Li, Xiaoxia Li, Weixuan Wu, Huadong Jiang, Yufen Zheng, Junjie Zhou, Xianmiao Ye, Junnan Lu, Wei Wang, Lei Yu, Yiping Li, Linbing Qu, Jianhua Wang, Feng Li, Ling Chen (), Linping Wu () and Liqiang Feng ()
Additional contact information
Xinglong Liu: Chinese Academy of Sciences
Zhengfeng Li: Chinese Academy of Sciences
Xiaoxia Li: Chinese Academy of Sciences
Weixuan Wu: Chinese Academy of Sciences
Huadong Jiang: Chinese Academy of Sciences
Yufen Zheng: Chinese Academy of Sciences
Junjie Zhou: Chinese Academy of Sciences
Xianmiao Ye: Sun Yat-sen University
Junnan Lu: Chinese Academy of Sciences
Wei Wang: Bioland Laboratory
Lei Yu: Guangzhou Medical University
Yiping Li: Sun Yat-sen University
Linbing Qu: Chinese Academy of Sciences
Jianhua Wang: Chinese Academy of Sciences
Feng Li: Guangzhou Medical University
Ling Chen: Chinese Academy of Sciences
Linping Wu: Chinese Academy of Sciences
Liqiang Feng: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/β receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53242-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53242-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53242-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().