tetano
Editor, Senior Moderator
Sci Immunol
. 2025 Oct 17;10(112):eadu4107.
doi: 10.1126/sciimmunol.adu4107. Epub 2025 Oct 10. Germinal center-mediated broadening of B cell responses to SARS-CoV-2 booster immunization
Sameer Kumar Malladi[SUP] 1 [/SUP], Deepika Jaiswal[SUP] 2 [/SUP], Baoling Ying[SUP] 3 [/SUP], Wafaa B Alsoussi[SUP] 1 [/SUP], Tamarand L Darling[SUP] 3 [/SUP], Bernadeta Dadonaite[SUP] 4 [/SUP], Alesandro Civljak[SUP] 2 [/SUP], Stephen C Horvath[SUP] 1 [/SUP], Julian Q Zhou[SUP] 1 [/SUP], Wooseob Kim[SUP] 1 5 [/SUP], Jackson S Turner[SUP] 1 [/SUP], Aaron J Schmitz[SUP] 1 [/SUP], Fangjie Han[SUP] 1 [/SUP], Suzanne M Scheaffer[SUP] 3 [/SUP], Christopher W Farnsworth[SUP] 1 [/SUP], Raffael Nachbagauer[SUP] 6 [/SUP], Biliana Nestorova[SUP] 6 [/SUP], Spyros Chalkias[SUP] 6 [/SUP], Michael K Klebert[SUP] 7 [/SUP], Darin K Edwards[SUP] 6 [/SUP], Robert Paris[SUP] 6 [/SUP], Benjamin S Strnad[SUP] 8 [/SUP], William D Middleton[SUP] 8 [/SUP], Jane A O'Halloran[SUP] 9 10 [/SUP], Rachel M Presti[SUP] 9 11 [/SUP], Jesse D Bloom[SUP] 4 12 [/SUP], Adrianus C M Boon[SUP] 1 3 13 [/SUP], Michael S Diamond[SUP] 1 3 11 13 14 [/SUP], Goran Bajic[SUP] 2 [/SUP], Ali H Ellebedy[SUP] 1 11 13 14 [/SUP]
Affiliations
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 IGHV3-66 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.
. 2025 Oct 17;10(112):eadu4107.
doi: 10.1126/sciimmunol.adu4107. Epub 2025 Oct 10. Germinal center-mediated broadening of B cell responses to SARS-CoV-2 booster immunization
Sameer Kumar Malladi[SUP] 1 [/SUP], Deepika Jaiswal[SUP] 2 [/SUP], Baoling Ying[SUP] 3 [/SUP], Wafaa B Alsoussi[SUP] 1 [/SUP], Tamarand L Darling[SUP] 3 [/SUP], Bernadeta Dadonaite[SUP] 4 [/SUP], Alesandro Civljak[SUP] 2 [/SUP], Stephen C Horvath[SUP] 1 [/SUP], Julian Q Zhou[SUP] 1 [/SUP], Wooseob Kim[SUP] 1 5 [/SUP], Jackson S Turner[SUP] 1 [/SUP], Aaron J Schmitz[SUP] 1 [/SUP], Fangjie Han[SUP] 1 [/SUP], Suzanne M Scheaffer[SUP] 3 [/SUP], Christopher W Farnsworth[SUP] 1 [/SUP], Raffael Nachbagauer[SUP] 6 [/SUP], Biliana Nestorova[SUP] 6 [/SUP], Spyros Chalkias[SUP] 6 [/SUP], Michael K Klebert[SUP] 7 [/SUP], Darin K Edwards[SUP] 6 [/SUP], Robert Paris[SUP] 6 [/SUP], Benjamin S Strnad[SUP] 8 [/SUP], William D Middleton[SUP] 8 [/SUP], Jane A O'Halloran[SUP] 9 10 [/SUP], Rachel M Presti[SUP] 9 11 [/SUP], Jesse D Bloom[SUP] 4 12 [/SUP], Adrianus C M Boon[SUP] 1 3 13 [/SUP], Michael S Diamond[SUP] 1 3 11 13 14 [/SUP], Goran Bajic[SUP] 2 [/SUP], Ali H Ellebedy[SUP] 1 11 13 14 [/SUP]
Affiliations
- PMID: 41071904
- DOI: 10.1126/sciimmunol.adu4107
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 IGHV3-66 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.