@article {Powell2020.08.28.272518, author = {Abigail E. Powell and Kaiming Zhang and Mrinmoy Sanyal and Shaogeng Tang and Payton A. Weidenbacher and Shanshan Li and Tho D. Pham and John E. Pak and Wah Chiu and Peter S. Kim}, title = {A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice}, elocation-id = {2020.08.28.272518}, year = {2020}, doi = {10.1101/2020.08.28.272518}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Development of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against COVID-19.Competing Interest StatementAEP and PSK are named as inventors on a provisional patent application applied for by Stanford University and the Chan Zuckerberg Biohub on immunogenic coronavirus fusion proteins and related methods.}, URL = {https://www.biorxiv.org/content/early/2020/08/28/2020.08.28.272518}, eprint = {https://www.biorxiv.org/content/early/2020/08/28/2020.08.28.272518.full.pdf}, journal = {bioRxiv} }