Protection against 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; 4-8 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 compared to sera from immunizations with homotypic SARS-CoV-2-RBD-nanoparticles or COVID-19 convalescent human plasmas. Moreover, sera from mosaic-RBD-immunized mice neutralized heterologous pseudotyped coronaviruses equivalently or better after priming than sera from homotypic SARS-CoV-2-RBD-nanoparticle immunizations, demonstrating no immunogenicity loss 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.

中文翻译：

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马赛克纳米颗粒在小鼠体内引发对人畜共患冠状病毒的交叉反应免疫反应

迫切需要针对 SARS-CoV-2 和 SARS 相关的突发人畜共患冠状病毒进行防护。我们制作了显示 SARS-CoV-2 受体结合域 (RBD) 的同型纳米粒子，或共同显示 SARS-CoV-2 RBD 以及来自动物 β 冠状病毒的 RBD，这些 RBD 对人类构成威胁（马赛克纳米粒子；4-8 个不同的 RBD） 。用 RBD 纳米颗粒而非可溶性抗原免疫的小鼠引发了交叉反应性结合和中和反应。与同型 SARS-CoV-2-RBD-纳米颗粒免疫血清或 COVID-19 康复期人血浆相比，Mosaic-RBD-纳米颗粒引发的抗体对异源 RBD 具有优异的交叉反应识别能力。此外，与同型 SARS-CoV-2-RBD 纳米颗粒免疫的血清相比，嵌合 RBD 免疫小鼠的血清在引发后中和异源假型冠状病毒的能力相同或更好，表明共展示不会导致针对特定 RBD 的免疫原性损失。使用嵌合 RBD 纳米颗粒进行单次免疫提供了一种同时预防 SARS-CoV-2 和新出现的人畜共患冠状病毒的潜在策略。