A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice
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.
Authors
- Junnan Lu
- Xianmiao Ye
- Linbing Qu (ORCID: https://orcid.org/0000-0002-3964-1740)
- Linping Wu (ORCID: https://orcid.org/0000-0001-7579-2987)
- Yufen Zheng (ORCID: https://orcid.org/0000-0002-5140-5521)
- Zhengfeng Li (ORCID: https://orcid.org/0000-0003-2878-8779)
- Huadong Jiang (ORCID: https://orcid.org/0000-0002-5854-7004)
- Yi‐Ping Li (ORCID: https://orcid.org/0000-0001-6011-3101)
- Liqiang Feng (ORCID: https://orcid.org/0000-0001-6811-2074)
- Junjie Zhou (ORCID: https://orcid.org/0000-0001-7758-4807)
- Xiaoxia Li (ORCID: https://orcid.org/0000-0001-5580-6261)
- Ling Chen (ORCID: https://orcid.org/0000-0003-1485-1626)
- Jianhua Wang (ORCID: https://orcid.org/0000-0002-2773-3429)
- Feng Li (ORCID: https://orcid.org/0000-0003-3169-6349)
- Weixuan Wu
- Lei Yu (ORCID: https://orcid.org/0000-0002-1597-8779)
- Xinglong Liu (ORCID: https://orcid.org/0000-0002-1215-4117)
- Wei Wang (ORCID: https://orcid.org/0000-0003-2044-6387)
Institutions
- University of Science and Technology of China (CN)
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN)
- Guangzhou Chemistry (China) (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Guangzhou Eighth People's Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41467-024-53242-0
- Citations
- 35
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 19.00
Funders
- State Key Laboratory of Respiratory Disease
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- China Postdoctoral Science Foundation
- Natural Science Foundation of Guangdong Province
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences