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TitleGerminal center-mediated broadening of B cell responses to SARS-CoV-2 booster immunization.
Journal, issue, pagesSci Immunol, Vol. 10, Issue 112, Page eadu4107, Year 2025
Publish dateOct 17, 2025
AuthorsSameer Kumar Malladi / Deepika Jaiswal / Baoling Ying / Wafaa B Alsoussi / Tamarand L Darling / Bernadeta Dadonaite / Alesandro Civljak / Stephen C Horvath / Julian Q Zhou / Wooseob Kim / Jackson S Turner / Aaron J Schmitz / Fangjie Han / Suzanne M Scheaffer / Christopher W Farnsworth / Raffael Nachbagauer / Biliana Nestorova / Spyros Chalkias / Michael K Klebert / Darin K Edwards / Robert Paris / Benjamin S Strnad / William D Middleton / Jane A O'Halloran / Rachel M Presti / Jesse D Bloom / Adrianus C M Boon / Michael S Diamond / Goran Bajic / Ali H Ellebedy /
PubMed AbstractGerminal centers (GCs) are key sites for antibody diversification and affinity maturation. SARS-CoV-2 messenger RNA (mRNA) vaccines elicit robust GC B cell responses in humans, but how these ...Germinal centers (GCs) are key sites for antibody diversification and affinity maturation. SARS-CoV-2 messenger RNA (mRNA) vaccines elicit robust GC B cell responses in humans, but how these responses influence the breadth of immunity against viral variants remains unclear. We analyzed GC B cell responses in nine healthy adults after mRNA booster immunization. We show that 77.8% of the B cell clones in the GC expressed representative monoclonal antibodies (mAbs) recognizing the spike protein, with 37.8% of these targeting the receptor binding domain (RBD). One RBD-targeting mAb, mAb-52, neutralized all tested SARS-CoV-2 strains, including the recent XEC variant. mAb-52 used the public clonotype, protected hamsters challenged against the EG.5.1 variant, and targeted the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Its broad reactivity was driven by extensive somatic hypermutation, underscoring the critical role of GC reactions in shaping cross-variant B cell immunity after SARS-CoV-2 booster vaccination.
External linksSci Immunol / PubMed:41071904
MethodsEM (single particle)
Resolution3.1 Å
Structure data

EMDB-47426, PDB-9e21:
CryoEM structure of a broadly neutralizing anti-SARS-CoV-2 antibody 52
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

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

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsIMMUNE SYSTEM / SARS-CoV-2 / Antibody / RBD / Viral protein-immune system complex

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