Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota, United States of America.
Center for Coronavirus Research, University of Minnesota, Saint Paul, Minnesota, United States of America.
PLoS Pathog. 2021 Sep 7;17(9):e1009897. doi: 10.1371/journal.ppat.1009897. eCollection 2021 Sep.
The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.
抗击 COVID-19 大流行及其潜在后果的关键是开发各种有效且安全的疫苗，这些疫苗能引发持久的免疫反应，并覆盖 SARS-CoV-2 的多种变体。重组病毒受体结合域（RBD）是安全的疫苗候选物，但由于缺乏类似病毒的免疫原展示模式，其通常效果有限。在此，我们开发了一种新型的病毒样纳米颗粒（VLP）疫苗，其表面展示有 120 个拷贝的 SARS-CoV-2 RBD。这种 VLP-RBD 疫苗在免疫原展示方面模拟了基于病毒的疫苗，从而提高了其效力，同时保持了基于蛋白质的亚单位疫苗的安全性。与 RBD 疫苗相比，VLP-RBD 疫苗在小鼠中诱导了五倍以上的中和抗体，能够有效阻止 SARS-CoV-2 与其宿主受体结合，并有效地中和变体 SARS-CoV-2 株、SARS-CoV-1 和 SARS-CoV-1 相关的蝙蝠冠状病毒的细胞进入。在为期两个月的研究期间，VLP-RBD 疫苗诱导的这些中和免疫反应并未减弱。此外，VLP-RBD 疫苗能有效保护小鼠免受 SARS-CoV-2 攻击，显著减少免疫小鼠中临床症状和病理变化的发展。VLP-RBD 疫苗为控制 SARS-CoV-2 的传播提供了一种潜在有效的解决方案。
