A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice
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.
- Authors:
-
- Stanford Univ., CA (United States). Dept. of Biochemistry & Stanford ChEM-H
- Stanford Univ., CA (United States). Dept. of Bioengineering & James H. Clark Center
- Stanford Univ., CA (United States). Dept. of Biochemistry & Stanford ChEM-H; Stanford Univ., CA (United States). Dept. of Chemistry
- Stanford Univ., CA (United States). Dept. of Pathology; Stanford Blood Center, Palo Alto, CA (United States)
- Chan Zuckerberg Biohub, San Francisco, California 94158, United States
- Stanford Univ., CA (United States). Dept. of Bioengineering & James H. Clark Center; Chan Zuckerberg Biohub, San Francisco, CA (United States); SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL), Division of CryoEM and Bioimaging
- Stanford Univ., CA (United States).Dept. of Biochemistry & Stanford ChEM-H; Chan Zuckerberg Biohub, San Francisco, CA (United States)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1778237
- Grant/Contract Number:
- AC02-76SF00515; DRG-2301-17; S10OD02160; P01AI120943; R01AI148382; P41GM103832
- Resource Type:
- Accepted Manuscript
- Journal Name:
- ACS Central Science
- Additional Journal Information:
- Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2374-7943
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Powell, Abigail E., Zhang, Kaiming, Sanyal, Mrinmoy, Tang, Shaogeng, Weidenbacher, Payton A., Li, Shanshan, Pham, Tho D., Pak, John E., Chiu, Wah, and Kim, Peter S. A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice. United States: N. p., 2021.
Web. doi:10.1021/acscentsci.0c01405.
Powell, Abigail E., Zhang, Kaiming, Sanyal, Mrinmoy, Tang, Shaogeng, Weidenbacher, Payton A., Li, Shanshan, Pham, Tho D., Pak, John E., Chiu, Wah, & Kim, Peter S. A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice. United States. https://doi.org/10.1021/acscentsci.0c01405
Powell, Abigail E., Zhang, Kaiming, Sanyal, Mrinmoy, Tang, Shaogeng, Weidenbacher, Payton A., Li, Shanshan, Pham, Tho D., Pak, John E., Chiu, Wah, and Kim, Peter S. Tue .
"A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice". United States. https://doi.org/10.1021/acscentsci.0c01405. https://www.osti.gov/servlets/purl/1778237.
@article{osti_1778237,
title = {A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice},
author = {Powell, Abigail E. and Zhang, Kaiming and Sanyal, Mrinmoy and Tang, Shaogeng and Weidenbacher, Payton A. and Li, Shanshan and Pham, Tho D. and Pak, John E. and Chiu, Wah and Kim, Peter S.},
abstractNote = {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.},
doi = {10.1021/acscentsci.0c01405},
journal = {ACS Central Science},
number = 1,
volume = 7,
place = {United States},
year = {Tue Jan 05 00:00:00 EST 2021},
month = {Tue Jan 05 00:00:00 EST 2021}
}
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