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

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A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice
ACS Central Science ( IF 12.7 ) Pub Date : 2021-01-05 , DOI: 10.1021/acscentsci.0c01405
Abigail E Powell ₁ , Kaiming Zhang ₂ , Mrinmoy Sanyal ₁ , Shaogeng Tang ₁ , Payton A Weidenbacher _{1,

3} , Shanshan Li ₂ , Tho D Pham _{4,

5} , John E Pak ₆ , Wah Chiu _{2,

6,

7} , Peter S Kim _{1,

6}

Affiliation

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.

中文翻译：

使用刺突功能化铁蛋白疫苗进行单次免疫可在小鼠体内引发针对 SARS-CoV-2 的中和抗体反应

开发安全有效的 SARS-CoV-2 疫苗是公共卫生的首要任务。我们使用自组装铁蛋白纳米颗粒设计了候选亚单位疫苗，该纳米颗粒显示两种多聚化 SARS-CoV-2 刺突之一：全长胞外域 (S-Fer) 或 C 端 70 个氨基酸缺失 (SΔC-Fer)。铁蛋白是一种用于生产疫苗的有吸引力的纳米颗粒平台，基于铁蛋白的疫苗已在两项独立的临床试验中进行了人体研究。我们通过冷冻电镜和与构象特异性单克隆抗体的结合证实了铁蛋白表面刺突的正确折叠和抗原性。用两种刺突铁蛋白颗粒中的任何一种对小鼠进行单次免疫后，慢病毒 SARS-CoV-2 假病毒检测显示，平均中和抗体滴度比 COVID-19 患者恢复期血浆中的平均中和抗体滴度高至少 2 倍。此外，与单独使用刺突受体结合域（RBD）单体或刺突胞外域三聚体进行免疫相比，单剂量的 SΔC-Fer 引发显着更高的中和反应。第二次给药后，用 SΔC-Fer 免疫的小鼠表现出比所有其他组更高的中和滴度。综上所述，这些结果表明，铁蛋白上 SARS-CoV-2 刺突的多价呈现可以显着增强中和抗体的引发，从而构成针对 COVID-19 的单剂量疫苗接种的可行策略。

更新日期：2021-01-27

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