GEO series

SARS-CoV-2 Variant Boosters and Breakthrough Infections Drive Functional Differences in the Memory B Cell Repertoire

GSE303324 Homo sapiens Expression profiling by high throughput sequencing; Other 55 samples Submitted 2026/06/01 Platform GPL24676

Summary

Evolving respiratory viruses such as influenza and COVID-19 cause seasonal respiratory illness and death. Updated vaccines with virus variants are made to increase efficacy, but pre-existing immunity affects the response. To understand if variant boosters modify the memory B cell (MBC) repertoire, we analyzed the human MBC response in the COVAIL vaccine trial where individuals previously vaccinated with COVID-19 prototype spike immunogens were boosted with prototype spike, variant spikes, or both. We analyzed the cross-reactivity, phenotype and functionality of the MBC response and determined that variant vaccine boosters led to greater recall of cross-reactive MBCs compared to a prototype but limited de novo variant-specific MBC responses. Some study participants also experienced breakthrough infections with SARS-CoV-2 Omicron variants after the vaccine boost that primarily expanded cross-reactive MBCs. These MBCs potently neutralized closely related Omicron virus strains, but displayed less breadth toward more distant Omicron subvariants than MBCs from uninfected individuals. Thus, infection can narrow the cross-reactivity of the memory B cell repertoire.

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Direct links to NCBI, no account and no request form: the whole study as GSE303324_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 55 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1294831 and SRA study SRP602725. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

30 conditions, each sampled once — no replicated groups

VRC-COVAIL-09-19-2023-VDJ-Pool ×3 VRC-COVAIL-09-20-2023-VDJ-Pool ×3 VRC-COVAIL-09-28-2023-VDJ-Pool ×3 VRC-COVAIL-09-21-2023-VDJ-Pool ×2 VRC-COVAIL-09-26-2023-VDJ-Pool ×2 VRC-COVAIL-09-27-2023-VDJ-Pool ×2 VRC-COVAIL-10-06-2023-VDJ-Pool ×2

Read from the first 40 of 55 sample titles: 30 distinct titles with little repetition. Check it against the sample list below before relying on it.

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