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<p>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.</p>

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Single-dose infusion of engineered viral receptor binding domain confers rapid and durable protection against viral infection

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月25日

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  • Haiqiao Sun,
  • Bei Tong,
  • Deshan Ren,
  • Ao Hu,
  • He Li,
  • Yixin Zhang,
  • Shuang Liu,
  • Xiang Duan,
  • Zijian Zhang,
  • Wei Liu,
  • Haokun Yang,
  • Jian Chen,
  • Tunyu Jian,
  • Huanying Zheng,
  • Bixia Ke,
  • Hanri Zeng,
  • Changwen Ke,
  • Xiaofang Peng,
  • Yongzhen Liu,
  • Kai Deng,
  • Xianchi Dong,
  • Yan Li

摘要

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.