A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice.

ACS Central Science
A. E. PowellPeter S. Kim

Abstract

The 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 mul...Continue Reading

Citations

Feb 16, 2021·Protein Science : a Publication of the Protein Society·Benjamin N BellPeter S Kim
May 1, 2021·Pharmaceuticals·Megan A YamoahXiao-Dong Zhang
Jun 1, 2021·ACS Central Science·Yingzhu LiQiongqiong Zhou

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Datasets Mentioned

BETA
MN9089473
MN908947.3
DQ168569
DQ168570
MT470196
MT599945
EMD-23220

Methods Mentioned

BETA
electron microscopy
size-exclusion
light scattering
dot blot
size-exclusion chromatography
light-scattering
affinity
glycosylation
enzyme-linked immunosorbent assays
ELISA

Clinical Trials Mentioned

NCT03186781
NCT03814720

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