tetano
Editor, Senior Moderator
ACS Cent Sci
. 2021 Jan 27;7(1):183-199.
doi: 10.1021/acscentsci.0c01405. Epub 2021 Jan 5.
A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice
Abigail E Powell[SUP] 1 [/SUP], Kaiming Zhang[SUP] 2 [/SUP], Mrinmoy Sanyal[SUP] 1 [/SUP], Shaogeng Tang[SUP] 1 [/SUP], Payton A Weidenbacher[SUP] 1 3 [/SUP], Shanshan Li[SUP] 2 [/SUP], Tho D Pham[SUP] 4 5 [/SUP], John E Pak[SUP] 6 [/SUP], Wah Chiu[SUP] 2 6 7 [/SUP], Peter S Kim[SUP] 1 6 [/SUP]
Affiliations
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 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.
. 2021 Jan 27;7(1):183-199.
doi: 10.1021/acscentsci.0c01405. Epub 2021 Jan 5.
A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice
Abigail E Powell[SUP] 1 [/SUP], Kaiming Zhang[SUP] 2 [/SUP], Mrinmoy Sanyal[SUP] 1 [/SUP], Shaogeng Tang[SUP] 1 [/SUP], Payton A Weidenbacher[SUP] 1 3 [/SUP], Shanshan Li[SUP] 2 [/SUP], Tho D Pham[SUP] 4 5 [/SUP], John E Pak[SUP] 6 [/SUP], Wah Chiu[SUP] 2 6 7 [/SUP], Peter S Kim[SUP] 1 6 [/SUP]
Affiliations
- PMID: 33527087
- PMCID: PMC7805605
- DOI: 10.1021/acscentsci.0c01405
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 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.