Designed mosaic nanoparticles enhance cross-reactive immune responses in mice

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Pub Date : 2025-01-23 DOI:10.1016/j.cell.2024.12.015

Eric Wang, Alexander A. Cohen, Luis F. Caldera, Jennifer R. Keeffe, Annie V. Rorick, Yusuf M. Adia, Priyanthi N.P. Gnanapragasam, Pamela J. Bjorkman, Arup K. Chakraborty

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引用次数: 0

Abstract

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2_COMs), five (mosaic-5_COM), or seven (mosaic-7_COM) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges. Naive and COVID-19 pre-vaccinated mice immunized with mosaic-7_COM elicited antibodies targeting conserved RBD epitopes, and their sera exhibited higher binding and neutralization titers against sarbecoviruses than mosaic-8b. Mosaic-2_COMs and mosaic-5_COM elicited higher antibody potencies against some SARS-CoV-2 variants than mosaic-7_COM. However, mosaic-7_COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons, supporting its use to protect against SARS-CoV-2 variants and zoonotic sarbecoviruses.

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设计的马赛克纳米颗粒增强小鼠的交叉反应性免疫反应

纳米颗粒疫苗显示了sars样冠状病毒（sarbecvirus）受体结合域（rbd）的组合，可以防止SARS-CoV-2变异和人畜共患的sarbecovirus向人类的溢出。利用计算方法，我们设计了SARS-CoV-2 rbd的变体，并选择了7种天然sarbecovirus rbd，每种rbd都能正确折叠并消除对可变表位的抗体反应。将rbd附着在60粒纳米颗粒上，使免疫原显示2个（mosaic- 2com）、5个（mosaic-5COM）或7个（mosaic-7COM）不同的rbd，与mosaic-8b进行比较，从而引发交叉反应抗体，保护动物免受sarbecvirus的攻击。用mosaic-7COM免疫的幼年和预接种COVID-19的小鼠可诱导针对保守RBD表位的抗体，其血清对sarbecovirus的结合和中和效价高于mosaic-8b。与mosaic-7COM相比，mosaic- 2com和mosaic-5COM对某些SARS-CoV-2变体的抗体效价更高。然而，mosaic-7COM对人畜共患的sarbecovirus和高度突变的Omicrons产生了更有效的反应，支持其用于预防SARS-CoV-2变体和人畜共患的sarbecovirus。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.