Published in Science Immunology – October 10, 2025

Article Title: Germinal center–mediated broadening of B cell responses to SARS-CoV-2 booster immunization

Bottom Line: Bivalent mRNA booster vaccination not only reactivates memory B cells against ancestral SARS-CoV-2 but also promotes their further maturation in germinal centers, leading to broader antibody protection against emerging viral variants.

Results: 

 Booster vaccination induced strong germinal center B cell responses driven largely by recall memory.

 Roughly 60% of receptor-binding domain (RBD)–binding clones were cross-reactive to Omicron variants.

 A broadly neutralizing antibody (mAb-52) neutralized all tested SARS-CoV-2 variants and protected animals.

 Cryo-EM analysis revealed that mAb-52 targets a conserved spike epitope, explaining its breadth.

Why the Research Is Interesting:  These results show that SARS-CoV-2 variant boosters expand the breadth of B cell immunity by activating and maturing cross-reactive memory B cells in germinal centers. This broadening of antibody responses is essential for durable protection as the virus continues to evolve.

Who: Healthy adult participants who received bivalent mRNA-1273.214 booster vaccination encoding the prefusion stabilized WA1/2020 (WA1) and BA.1 spike proteins.

When: Samples were collected in the spring of 2022, when Omicron subvariants BA.1 and BA.2 were predominant.

What: Immune response to the bivalent variant booster vaccine focused on GC B cells, breadth of antibody neutralization, and structural characterization of broadly neutralizing antibody mAb-52 binding to the SARS-CoV-2 spike.

How: Single-cell RNA and B cell receptor sequencing, neutralization assays, animal challenge experiments, and cryo-electron microscopy structural analysis were performed to characterize B cell responses, antibody efficacy, and the structural basis of broad neutralization.

Study Conclusions: Bivalent mRNA booster vaccination recruits recall memory B cells into germinal centers, driving the expansion of broadly neutralizing antibodies that can target diverse SARS-CoV-2 variants, including emerging Omicron lineages. Structural analysis of one such antibody revealed a conserved spike epitope shared across variants, providing a basis for broad neutralization. These findings highlight the essential role of germinal centers in shaping durable, cross-variant B cell immunity and support the continued use of variant boosters as the virus evolves.

Corresponding Author:  Goran Bajic, PhD, Icahn School of Medicine at Mount Sinai

Said Mount Sinai’s Dr. Goran Bajic of the research: “SARS-CoV-2 variant boosters predominantly recruit recall memory B cells into germinal centers, driving the generation of broadly neutralizing antibodies,” said Dr. Goran Bajic of Mount Sinai. “These findings underscore the critical role of germinal centers in long-term vaccine effectiveness and inform strategies for designing next-generation vaccines.”

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