Open AccessA Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice
Author(s) -
Alex Chen,
Kaiming Zhang,
Mrinmoy Sanyal,
Shaogeng Tang,
Payton A. Weidenbacher,
Shanshan Li,
Tho Pham,
John E. Pak,
Wah Chiu,
Peter S. Kim
Publication year - 2021
Publication title -
acs central science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.893
H-Index - 76
eISSN - 2374-7951
pISSN - 2374-7943
DOI - 10.1021/acscentsci.0c01405
Subject(s) - ectodomain , ferritin , neutralizing antibody , antibody , virology , immunization , chemistry , antigenicity , vaccination , monoclonal antibody , biology , virus , receptor , immunology , biochemistry
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 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.