Single-dose infusion of engineered viral receptor binding domain confers rapid and durable protection against viral infection
Developing both rapid- and long-acting antiviral drugs for single-dose administration can improve medication adherence and protect people at risk of infection. To provide proof of this concept, here, we designed multimerized form of viral receptor-binding domains (RBDs) to immediately occupy viral receptors to block infection and subsequently induce virus-specific protective immunity. We engineered SARS-CoV-2 RBD, enhancing its affinity to ACE2 and immunogenicity through multimerization and Fc modification. A single administration of 4RBD-Fc not only effectively blocked ACE2-dependent SARS-CoV-2 infections but also elicited robust virus-specific mucosal and systemic immunity in the absence of adjuvants, providing superior early and long-lasting protection compared to adjuvanted vaccines in mice. These findings demonstrate the feasibility and efficacy of engineered viral RBD as immediate-acting and long-lasting single-dose antiviral drugs through rapid receptor blocking and ensuing adaptive immunity induction.
Authors
- Xiao-Fang Peng (ORCID: https://orcid.org/0000-0002-1956-4151)
- Huanying Zheng (ORCID: https://orcid.org/0000-0002-2928-548X)
- Tunyu Jian (ORCID: https://orcid.org/0000-0002-9814-500X)
- Haiqiao Sun (ORCID: https://orcid.org/0009-0005-2573-9842)
- Bei Tong (ORCID: https://orcid.org/0000-0002-6863-6019)
- Kai Deng (ORCID: https://orcid.org/0000-0002-9973-8130)
- Li He (ORCID: https://orcid.org/0000-0001-9313-1218)
- Deshan Ren (ORCID: https://orcid.org/0000-0001-5983-8068)
- Huimin Yang (ORCID: https://orcid.org/0000-0002-4476-2416)
- Shuang Liu (ORCID: https://orcid.org/0000-0001-6306-6929)
- Zijian Zhang (ORCID: https://orcid.org/0000-0001-9000-4678)
- Yixin Zhang (ORCID: https://orcid.org/0009-0008-6685-0610)
- Yan Li (ORCID: https://orcid.org/0000-0001-7612-3953)
- Jian Chen (ORCID: https://orcid.org/0000-0002-5567-2280)
- Changwen Ke
- Yongzhen Liu (ORCID: https://orcid.org/0000-0002-5003-1484)
- Hanri Zeng
- Bixia Ke
- Xiang Duan
- Wei Liu (ORCID: https://orcid.org/0009-0001-6937-2430)
- Xianchi Dong
- Andrew C. Hu
Institutions
- Sun Yat-sen University (CN)
- China Pharmaceutical University (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Model Animal Research Center (CN)
- Guangdong Provincial Center for Disease Control and Prevention (CN)
- Institute of Botany (CN)
- Wuxi Institute of Technology (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-08-25
- DOI
- https://doi.org/10.1038/s42003-025-08704-6
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Natural Science Foundation of Guangdong Province
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities