Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Science. 2021 Feb 12;371(6530):735-741. doi: 10.1126/science.abf6840. Epub 2021 Jan 12.
Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles with four to eight distinct RBDs). Mice immunized with RBD nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic RBD nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs relative to sera from immunizations with homotypic SARS-CoV-2-RBD nanoparticles or COVID-19 convalescent human plasmas. Moreover, after priming, sera from mosaic RBD-immunized mice neutralized heterologous pseudotyped coronaviruses as well as or better than sera from homotypic SARS-CoV-2-RBD nanoparticle immunizations, demonstrating no loss of immunogenicity against particular RBDs resulting from co-display. A single immunization with mosaic RBD nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.
迫切需要针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 和与 SARS 相关的新兴动物源性冠状病毒的保护。我们制备了展示 SARS-CoV-2 受体结合域 (RBD) 的同型纳米颗粒,或者共展示 SARS-CoV-2 RBD 以及代表人类威胁的动物贝塔冠状病毒的 RBD(具有四个到八个不同 RBD 的嵌合纳米颗粒)。用 RBD 纳米颗粒免疫的小鼠,而不是可溶性抗原,可引发交叉反应性结合和中和反应。与用同型 SARS-CoV-2-RBD 纳米颗粒或 COVID-19 恢复期人类血浆免疫的血清相比,嵌合 RBD 纳米颗粒诱导的抗体对异源 RBD 具有更好的交叉反应性识别。此外,在进行初次免疫后,来自嵌合 RBD 免疫的小鼠的血清可中和异源假型冠状病毒,其效果与用同型 SARS-CoV-2-RBD 纳米颗粒免疫的血清相当,甚至更好,表明共展示不会导致针对特定 RBD 的免疫原性丧失。单次接种嵌合 RBD 纳米颗粒可能是一种同时预防 SARS-CoV-2 和新兴动物源性冠状病毒的策略。
Proc Natl Acad Sci U S A. 2025-5-27
Emerg Microbes Infect. 2020-12
Int J Nanomedicine. 2025-8-6
Nat Mater. 2025-7-31
J Exp Med. 2025-10-6
Angew Chem Int Ed Engl. 2021-1-4
Science. 2020-7-23