Computationally designed proteins mimic antibody immune evasion in viral evolution
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.
Authors
- Kelly P. Brock
- Aaron W. Kollasch (ORCID: https://orcid.org/0000-0001-9733-8822)
- Nicole N. Thadani (ORCID: https://orcid.org/0000-0002-4866-9294)
- Sandra Dross (ORCID: https://orcid.org/0000-0003-1013-6828)
- Javier A. Jaimes (ORCID: https://orcid.org/0000-0001-6706-092X)
- Alexander A. Cohen (ORCID: https://orcid.org/0000-0002-2818-656X)
- Ann Dauphin (ORCID: https://orcid.org/0000-0002-3570-8610)
- Jesse H. Erasmus (ORCID: https://orcid.org/0000-0003-1612-2697)
- Debora S. Marks (ORCID: https://orcid.org/0000-0001-9388-2281)
- Fadi Ghantous (ORCID: https://orcid.org/0000-0002-6772-6901)
- Jacob E. Lemieux (ORCID: https://orcid.org/0000-0002-2758-4005)
- Sarah F. Gurev (ORCID: https://orcid.org/0000-0001-5931-6622)
- Amy C Sherman (ORCID: https://orcid.org/0000-0002-6075-3990)
- Pascal Notin (ORCID: https://orcid.org/0000-0002-1877-8983)
- Pamela J. Björkman (ORCID: https://orcid.org/0000-0002-2277-3990)
- Leonid Yurkovetskiy (ORCID: https://orcid.org/0000-0001-5078-493X)
- DEBORAH HEYDENBURG FULLER (ORCID: https://orcid.org/0000-0001-7315-2441)
- Michael S. Seaman (ORCID: https://orcid.org/0000-0001-6444-3562)
- Jeremy Luban (ORCID: https://orcid.org/0000-0001-5650-4054)
- Noor Youssef (ORCID: https://orcid.org/0000-0002-7708-982X)
- Ben Kotzen
- Ralph Estanboulieh
- Daria Soto
Institutions
- Broad Institute (US)
- California Institute of Technology (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- University of Washington (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Center for Systems Biology (US)
Publication Details
- Journal
- Immunity
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1016/j.immuni.2025.04.015
- Citations
- 10
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 13.96
Funders
- Foundation for the National Institutes of Health
- Brigham and Women's Hospital
- Coalition for Epidemic Preparedness Innovations
- Massachusetts Consortium on Pathogen Readiness
- National Institutes of Health