Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection

Geng, Qibin; Tai, Wanbo; Baxter, Victoria K.; Shi, Juan; Wan, Yushun; Zhang, Xiujuan; Montgomery, Stephanie A.; Taft-Benz, Sharon A.; Anderson, Elizabeth J.; Knight, Audrey C.; Dinnon, Kenneth H.; Leist, Sarah R.; Baric, Ralph S.; Shang, Jian; Hong, Sung-Wook; Drelich, Aleksandra; Tseng, Chien-Te K.; Jenkins, Marc; Heise, Mark; Du, Lanying; Li, Fang

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.