美国麻省理工学院Arup K. Chakraborty等研究人员合作发现，设计的马赛克纳米颗粒可增强小鼠的交叉反应性免疫反应。相关论文于2025年1月23日在线发表于国际学术期刊《细胞》。

研究人员表示，展示组合型SARS类β冠状病毒（sarbecovirus）受体结合域（RBD）的纳米颗粒疫苗可能对SARS-CoV-2变种和动物源性sarbecovirus跨种传播到人类提供保护。

通过计算方法，研究人员设计了SARS-CoV-2 RBD的变体，并选择了7种天然sarbecovirus RBD，每种都预测能正确折叠并抑制对变异表位的抗体反应。将RBD连接到60-mer纳米颗粒上，研究人员制成展示两种（mosaic-2COM）、五种（mosaic-5COM）或七种（mosaic-7COM）不同RBD的免疫原，并与能够诱导交叉反应性抗体并保护动物免受sarbecovirus挑战的mosaic-8b进行比较。

研究人员用mosaic-7COM免疫的未感染小鼠和COVID-19预接种小鼠产生了针对保守RBD表位的抗体，并且其血清对sarbecovirus的结合和中和滴度高于mosaic-8b。mosaic-2COM和mosaic-5COM对某些SARS-CoV-2变种诱导的抗体效力高于mosaic-7COM。然而，mosaic-7COM对动物源性sarbecovirus和高度突变的Omicron变种诱导了更强的免疫反应，支持其用于保护免受SARS-CoV-2变种和动物源性sarbecovirus的感染。

附：英文原文

Title: Designed mosaic nanoparticles enhance cross-reactive immune responses in mice

Author: 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

Issue&Volume: 2025-01-23

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-2COMs), five (mosaic-5COM), or seven (mosaic-7COM) 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-7COM elicited antibodies targeting conserved RBD epitopes, and their sera exhibited higher binding and neutralization titers against sarbecoviruses than mosaic-8b. Mosaic-2COMs and mosaic-5COM elicited higher antibody potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons, supporting its use to protect against SARS-CoV-2 variants and zoonotic sarbecoviruses.

DOI: 10.1016/j.cell.2024.12.015

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01428-4