A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

BioRxiv : the Preprint Server for Biology
Abigail E PowellPeter S Kim

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 (S{Delta}C-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 S{Delta}C-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 S{Delta}C-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonst...Continue Reading

Datasets Mentioned

BETA
MN9089473
MN908947.3
DQ168569
DQ168570
MT470196
MT599945

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

Software Mentioned

CTFFIND4
cryoSPARC
MotionCor2
IDT Codon Optimization Tool
UCSF Chimera
EMAN2
ImageJ
GraphPad Prism
Relion
Fiji

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