TY - JOUR
T1 - Germinal center–mediated broadening of B cell responses to SARS-CoV-2 booster immunization
AU - Malladi, Sameer Kumar
AU - Jaiswal, Deepika
AU - Ying, Baoling
AU - Alsoussi, Wafaa B.
AU - Darling, Tamarand L.
AU - Dadonaite, Bernadeta
AU - Civljak, Alesandro
AU - Horvath, Stephen C.
AU - Zhou, Julian Q.
AU - Kim, Wooseob
AU - Turner, Jackson S.
AU - Schmitz, Aaron J.
AU - Han, Fangjie
AU - Scheaffer, Suzanne M.
AU - Farnsworth, Christopher W.
AU - Nachbagauer, Raffael
AU - Nestorova, Biliana
AU - Chalkias, Spyros
AU - Klebert, Michael K.
AU - Edwards, Darin K.
AU - Paris, Robert
AU - Strnad, Benjamin S.
AU - Middleton, William D.
AU - O’Halloran, Jane A.
AU - Presti, Rachel M.
AU - Bloom, Jesse D.
AU - Boon, Adrianus C.M.
AU - Diamond, Michael S.
AU - Bajic, Goran
AU - Ellebedy, Ali H.
N1 - Publisher Copyright:
© 2025, Author.
PY - 2025/10
Y1 - 2025/10
N2 - 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 mono clonal antibodies (mAbs) recognizing the spike protein, with 37.8% of these targeting the receptor binding do main (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.
AB - 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 mono clonal antibodies (mAbs) recognizing the spike protein, with 37.8% of these targeting the receptor binding do main (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.
UR - https://www.scopus.com/pages/publications/105018398395
U2 - 10.1126/sciimmunol.adu4107
DO - 10.1126/sciimmunol.adu4107
M3 - Article
C2 - 41071904
AN - SCOPUS:105018398395
SN - 2470-9468
VL - 10
JO - Science immunology
JF - Science immunology
IS - 112
M1 - eadu4107
ER -