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Sci Transl Med . SARS-CoV-2 variant booster vaccination and infection alter the breadth of the memory B cell repertoire

tetano

Editor, Senior Moderator
Sci Transl Med


. 2026 Jun 10;18(853):eaeb9847.
doi: 10.1126/scitranslmed.aeb9847. Epub 2026 Jun 10.
SARS-CoV-2 variant booster vaccination and infection alter the breadth of the memory B cell repertoire

Rory Malek[SUP] 1 [/SUP], Flavio Matassoli[SUP] 1 [/SUP], Kyle Gordon[SUP] 1 [/SUP], Geoffrey D Shimberg[SUP] 1 [/SUP], Grace E Mantus[SUP] 1 [/SUP], Abby Spangler[SUP] 1 [/SUP], Ankita J Chopde[SUP] 1 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], Bob C Lin[SUP] 1 [/SUP], Robin Carroll[SUP] 1 [/SUP], Rachel Kazmierski[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Christine M Posavad[SUP] 2 3 [/SUP], Nadine G Rouphael[SUP] 4 [/SUP], Angela R Branche[SUP] 5 [/SUP], Paul C Roberts[SUP] 6 [/SUP], Leonid Serebryannyy[SUP] 1 [/SUP], Sarah F Andrews[SUP] 1 [/SUP]


Affiliations
Abstract

Evolving endemic viruses such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain major health threats. Although variant updated vaccines aim to enhance protection, preexisting immunity shapes memory B cell (MBC) responses. To assess how SARS-CoV-2 spike protein variant-based vaccine boosters and infections alter the MBC repertoire, we analyzed MBC responses in the COVAIL vaccine trial, where participants previously vaccinated with SARS-CoV-2 Wuhan-1 spike immunogen were boosted with Wuhan-1, variant, or bivalent spike immunogens. Some participants also experienced a subsequent infection with an Omicron variant. We determined that variant vaccine boosters and SARS-CoV-2 infections led to transiently greater recall of cross-reactive MBCs compared with a Wuhan-1 vaccine booster. Long term, we detected little change in the MBC repertoire after an Omicron vaccine booster, but MBCs evaluated several months after Omicron variant infection had higher neutralization capacity to both Wuhan-1 and BA.1 compared with those from individuals who had not experienced an infection. However, these Wuhan-1/BA.1 cross-reactive MBCs from infected individuals displayed less breadth toward the more distant BA.2.86 lineage than MBCs from uninfected individuals. Thus, SARS-CoV-2 variant boosters and infections differentially shape the long-term MBC repertoire.


 
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