Youssef Noor, Gurev Sarah, Ghantous Fadi, Brock Kelly P, Jaimes Javier A, Thadani Nicole N, Dauphin Ann, Sherman Amy C, Yurkovetskiy Leonid, Soto Daria, Estanboulieh Ralph, Kotzen Ben, Notin Pascal, Kollasch Aaron W, Cohen Alexander A, Dross Sandra E, Erasmus Jesse, Fuller Deborah H, Bjorkman Pamela J, Lemieux Jacob E, Luban Jeremy, Seaman Michael S, Marks Debora S
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA.
Immunity. 2025 Jun 10;58(6):1411-1421.e6. doi: 10.1016/j.immuni.2025.04.015. Epub 2025 May 8.
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.
病毒感染的反复浪潮需要能对新出现的病毒保持有效的疫苗和治疗方法。我们目前评估干预措施的能力仅限于针对过去或正在传播的病毒变体进行评估，与未来的变体相比，这些变体在免疫逃逸潜力方面可能有所不同。为了解决这个问题，我们开发了EVE-Vax，这是一种用于设计抗原的计算方法，可预测未来病毒变体中观察到的免疫逃逸。我们设计了83种SARS-CoV-2刺突蛋白，这些蛋白可转导ACE2阳性细胞，并表现出与在COVID-19大流行中出现长达12个月后的变体相当的中和抗性。设计的刺突蛋白预示了后期变体中抗体从B.1-BA.4/5二价加强疫苗血清中的逃逸。与基于mRNA的加强疫苗相比，设计的构建体还突出了在非人类灵长类动物中基于纳米颗粒的加强疫苗引发的中和广度增加。我们的方法提供了靶向的合成蛋白组，可绘制免疫图谱，用于针对未来病毒株的早期疫苗和治疗评估。
