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镶嵌纳米颗粒在小鼠中引发针对人畜共患冠状病毒的交叉反应性免疫应答。

Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice.

作者信息

Cohen Alexander A, Gnanapragasam Priyanthi N P, Lee Yu E, Hoffman Pauline R, Ou Susan, Kakutani Leesa M, Keeffe Jennifer R, Wu Hung-Jen, Howarth Mark, West Anthony P, Barnes Christopher O, Nussenzweig Michel C, Bjorkman Pamela J

机构信息

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.

出版信息

bioRxiv. 2021 Jan 5:2020.11.17.387092. doi: 10.1101/2020.11.17.387092.

DOI:10.1101/2020.11.17.387092
PMID:33236016
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7685334/
Abstract

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.

摘要

迫切需要对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）和与SARS相关的新发人畜共患冠状病毒提供防护。我们制备了展示SARS-CoV-2受体结合域（RBD）的同型纳米颗粒，或同时展示SARS-CoV-2 RBD以及来自动物β冠状病毒且对人类构成威胁的RBD的纳米颗粒（嵌合纳米颗粒；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。与用同型SARS-CoV-2-RBD纳米颗粒免疫或COVID-19康复期人血浆免疫产生的血清相比，嵌合RBD纳米颗粒引发的抗体对异源RBD具有更强的交叉反应性识别能力。此外，与同型SARS-CoV-2-RBD纳米颗粒免疫产生的血清相比，嵌合RBD免疫小鼠的血清在初次免疫后对异源假型冠状病毒的中和能力相当或更强，这表明共展示不会导致对特定RBD的免疫原性丧失。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和新发人畜共患冠状病毒的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/75527c54aaa6/nihpp-2020.11.17.387092-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/cae5eabd6e98/nihpp-2020.11.17.387092-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/e29443c84e4b/nihpp-2020.11.17.387092-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/df20944aaa46/nihpp-2020.11.17.387092-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/75527c54aaa6/nihpp-2020.11.17.387092-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/cae5eabd6e98/nihpp-2020.11.17.387092-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/e29443c84e4b/nihpp-2020.11.17.387092-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/df20944aaa46/nihpp-2020.11.17.387092-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8252/7814406/75527c54aaa6/nihpp-2020.11.17.387092-f0004.jpg

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