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TitleA single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice.
Journal, issue, pagesbioRxiv, Year 2020
Publish dateAug 28, 2020
AuthorsAbigail E Powell / Kaiming Zhang / Mrinmoy Sanyal / Shaogeng Tang / Payton A Weidenbacher / Shanshan Li / Tho D Pham / John E Pak / Wah Chiu / Peter S Kim /
PubMed AbstractDevelopment 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 ...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.
External linksbioRxiv / PubMed:32869030 / PubMed Central
MethodsEM (single particle)
Resolution13.5 Å
Structure data

EMDB-23220:
Spike-Ferritin nanoparticle
Method: EM (single particle) / Resolution: 13.5 Å

Source
  • Severe acute respiratory syndrome coronavirus 2

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