Twenty-year persistence of SARS-CoV-1 immune imprinting shapes antibody responses to SARS-CoV-2 infection.

Durable antibody imprinting from SARS-CoV-1 persists for 20 years and shapes SARS-CoV-2 BF.7 breakthrough responses, with ~60% of monoclonals remaining SARS-1 imprinted.

• Why it matters: Long-term epitope specificity after sequential coronavirus infections is unclear, limiting how well immune imprinting can inform durable protection and vaccine design.
• What they did: Individuals sequentially infected with SARS-CoV-1 and SARS-CoV-2 were followed over two decades; monoclonal antibodies were profiled for SARS-1 versus SARS-2 epitope targeting, including neutralization and hamster protection.
• The result: About 37% of monoclonals overcame imprinting to target the SARS-2 receptor-binding motif overlapping the ACE2-binding site, and THZ937 protected hamsters against contact and airborne transmission of Omicron EG.5.1.

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