哈佛大学和麻省理工学院的布罗德研究所Debora S. Marks小组近日取得一项新成果。经过不懈努力，他们报道了计算设计的蛋白质模拟病毒进化中的抗体免疫逃避。2025年5月8日出版的《免疫学》杂志发表了这项成果。

为了解决这个问题，课题组人员开发了EVE-Vax，这是一种设计抗原的计算方法，预示着在未来的病毒变异中观察到的免疫逃逸。课题组人员设计了83种SARS-CoV-2刺突蛋白，它们转导ACE2阳性细胞，并表现出与长达12个月后在COVID-19大流行中出现的变体相当的中和抗性。设计的刺突预示着抗体会从B.1-BA.4/5二价加强血清中逃逸，这在后来的变体中有所体现。在非人灵长类动物中，与基于mRNA的助推器相比，基于纳米颗粒的助推器也突出了增加的中和广度。他们的方法提供了有针对性的合成蛋白面板，为早期疫苗和针对未来病毒株的治疗性评估绘制免疫景观图。

据了解，反复出现的病毒感染浪潮需要对新出现的病毒主题仍然有效的疫苗和治疗方法。他们评估干预措施的能力目前仅限于对过去或流行变异的评估，与未来变异相比，这些变异的免疫逃逸潜力可能有所不同。

附：英文原文

Title: Computationally designed proteins mimic antibody immune evasion in viral evolution

Author: Noor Youssef, Sarah Gurev, Fadi Ghantous, Kelly P. Brock, Javier A. Jaimes, Nicole N. Thadani, Ann Dauphin, Amy C. Sherman, Leonid Yurkovetskiy, Daria Soto, Ralph Estanboulieh, Ben Kotzen, Pascal Notin, Aaron W. Kollasch, Alexander A. Cohen, Sandra E. Dross, Jesse Erasmus, Deborah H. Fuller, Pamela J. Bjorkman, Jacob E. Lemieux, Jeremy Luban, Michael S. Seaman, Debora S. Marks

Issue&Volume: 2025-05-08

Abstract: Recurrent waves of viral infection necessitate vaccines and therapeutics that remain effective against emerging viruses. Our ability to evaluate interventions is currently limited to assessments against past or circulating variants, which likely differ in their immune escape potential compared with future variants. To address this, we developed EVE-Vax, a computational method for designing antigens that foreshadow immune escape observed in future viral variants. We designed 83 SARS-CoV-2 spike proteins that transduced ACE2-positive cells and displayed neutralization resistance comparable to variants that emerged up to 12 months later in the COVID-19 pandemic. Designed spikes foretold antibody escape from B.1-BA.4/5 bivalent booster sera seen in later variants. The designed constructs also highlighted the increased neutralization breadth elicited by nanoparticle-based, compared with mRNA-based, boosters in non-human primates. Our approach offers targeted panels of synthetic proteins that map the immune landscape for early vaccine and therapeutic evaluation against future viral strains.

DOI: 10.1016/j.immuni.2025.04.015

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00178-5