PT  - JOURNAL ARTICLE
AU  - Young-Il Kim
AU  - Dokyun Kim
AU  - Kwang-Min Yu
AU  - Hogyu David Seo
AU  - Shin-Ae Lee
AU  - Mark Anthony B. Casel
AU  - Seung-Gyu Jang
AU  - Stephanie Kim
AU  - WooRam Jung
AU  - Chih-Jen Lai
AU  - Young Ki Choi
AU  - Jae U. Jung
TI  - Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets
AID  - 10.1101/2021.01.28.428743
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.28.428743
4099  - http://biorxiv.org/content/early/2021/01/29/2021.01.28.428743.short
4100  - http://biorxiv.org/content/early/2021/01/29/2021.01.28.428743.full
AB  - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 pandemic, enters host cells via the interaction of its Receptor-Binding Domain (RBD) of Spike protein with host Angiotensin-Converting Enzyme 2 (ACE2). Therefore, RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling H. pylori-bullfrog ferritin nanoparticles as an antigen delivery. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. 16-20 months-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD-nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD-nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss and clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious viruses in nasal washes and lungs as well as viral RNA in respiratory organs. This study demonstrates the Spike RBD-nanoparticle as an effective protein vaccine candidate against SARS-CoV-2.