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

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.

doi:10.1021/acscentsci.0c01405

DOE OSTI · 1778237

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

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.

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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.

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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.. 2021-01-05. A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice. https://doi.org/10.1021/acscentsci.0c01405

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