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TitleTwenty-year persistence of SARS-CoV-1 immune imprinting shapes antibody responses to SARS-CoV-2 infection.
Journal, issue, pagesImmunity, Year 2026
Publish dateSep 7, 2026
AuthorsQi Zhang / Peng Chen / Fenglin Guo / Runhong Zhou / Ruihan Guo / Xiaofei Ge / Qianqian Yang / Xin Xie / Wei Xia / Junping Fan / Ziqing Yang / Yan Xu / Huiyu Huang / Jinqian Li / Han Wang / Huiyu Liao / Xuanling Shi / Na Liu / Yuting Chen / Zhiwei Chen / Jianzhu Ma / Xinquan Wang / Tong Zhang / Linqi Zhang /
PubMed AbstractAntibody imprinting is well recognized, yet its long-term dynamics and epitope specificity remain poorly understood. Here, we studied individuals sequentially infected with SARS-CoV-1 (SARS-1) and ...Antibody imprinting is well recognized, yet its long-term dynamics and epitope specificity remain poorly understood. Here, we studied individuals sequentially infected with SARS-CoV-1 (SARS-1) and SARS-CoV-2 (SARS-2) over two decades and found durable imprinting of antibody responses following SARS-2 BF.7 breakthrough infection. Approximately 60% of isolated monoclonal antibodies were SARS-1 imprinted and targeted conserved receptor-binding domain regions, whereas 37% overcame imprinting to recognize the SARS-2 receptor-binding motif overlapping the ACE2-binding site. Notably, some SARS-1-only antibodies retained germline-like features and neutralizing activity 20 years after infection. One exceptionally imprinted broadly neutralizing antibody, THZ937, protected hamsters against contact and airborne transmission of Omicron EG.5.1, demonstrating the functional relevance of durable imprinted antibodies. Together, these findings define the remarkable longevity and molecular basis of antibody imprinting and provide insights for pan-sarbecovirus vaccine design.
External linksImmunity / PubMed:42705227
MethodsEM (single particle) / X-ray diffraction
Resolution2.78 - 3.54 Å
Structure data

68583

22pd

EMDB-68583, PDB-22pd:
Cryo EM structure of SARS-COV-2 (BA.4) RBD in complex with THZ937 Fab (local refine)
Method: EM (single particle) / Resolution: 2.95 Å

PDB-45ic:
Complex structure of THZ-65 Fab bound to SARS-CoV-1 RBD
Method: X-RAY DIFFRACTION / Resolution: 2.78 Å

PDB-45id:
Complex structure of THZ-939 Fab bound to SARS-CoV-2 WT RBD
Method: X-RAY DIFFRACTION / Resolution: 3.54 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • severe acute respiratory syndrome coronavirus
  • homo sapiens (human)
  • severe acute respiratory syndrome-related coronavirus
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2;antibody; / VIRAL PROTEIN-IMMUNE SYSTEM complex / SARS-CoV-1 / complex / antibody / RBD / SARS-CoV-2

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