Med
Volume 3, Issue 7, 8 July 2022, Pages 468-480.e5
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Clinical and Translational Article
B cell-derived cfDNA after primary BNT162b2 mRNA vaccination anticipates memory B cells and SARS-CoV-2 neutralizing antibodies

https://doi.org/10.1016/j.medj.2022.05.005Get rights and content
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Highlights

  • cfDNA-based monitoring of immune cell turnover following SARS-CoV-2 vaccination

  • B cell cfDNA levels correlate with neutralizing antibodies and memory B cell counts

  • Lymphocyte and monocyte cfDNA levels are dramatically elevated after the booster

Context and significance

To understand the turnover of immune cells following SARS-CoV-2 vaccination, Fox-Fisher et al. analyzed fragments of cell-free DNA (cfDNA) that are released from dying immune cells to blood. The levels of B cell cfDNA after the primary dose correlated with neutralizing antibodies and memory B cells after the booster, revealing that early B cell turnover—potentially reflecting affinity maturation—affects later development of effective antibodies. They also observed co-elevation of lymphocyte and monocyte cfDNA after the booster, underscoring the involvement of innate immune cell turnover in the development of humoral and cellular adaptive immunity. cfDNA biomarkers open a new window into human immune cell dynamics in response to perturbations.

Abstract

Background

Much remains unknown regarding the response of the immune system to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination.

Methods

We employed circulating cell-free DNA (cfDNA) to assess the turnover of specific immune cell types following administration of the Pfizer/BioNTech vaccine.

Findings

The levels of B cell cfDNA after the primary dose correlated with development of neutralizing antibodies and memory B cells after the booster, revealing a link between early B cell turnover—potentially reflecting affinity maturation—and later development of effective humoral response. We also observed co-elevation of B cell, T cell, and monocyte cfDNA after the booster, underscoring the involvement of innate immune cell turnover in the development of humoral and cellular adaptive immunity. Actual cell counts remained largely stable following vaccination, other than a previously demonstrated temporary reduction in neutrophil and lymphocyte counts.

Conclusions

Immune cfDNA dynamics reveal the crucial role of the primary SARS-CoV-2 vaccine in shaping responses of the immune system following the booster vaccine.

Funding

This work was supported by a generous gift from Shlomo Kramer. Supported by grants from Human Islet Research Network (HIRN UC4DK116274 and UC4DK104216 to R.S. and Y.D.), Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, The Alex U Soyka Pancreatic Cancer Fund, The Israel Science Foundation, the Waldholtz/Pakula family, the Robert M. and Marilyn Sternberg Family Charitable Foundation, the Helmsley Charitable Trust, Grail, and the DON Foundation (to Y.D.). Y.D. holds the Walter and Greta Stiel Chair and Research Grant in Heart Studies. I.F.-F. received a fellowship from the Glassman Hebrew University Diabetes Center.

Keywords

BNT162b2
SARS-CoV-2
mRNA vaccine
cfDNA
liquid biopsy
DNA methylation
tissue dynamics
neutralizing antibody
memory B-cell

CAT scale

Translation to patients

Data and code availability

  • All data reported in this paper is included in the Data S1 and will be shared by the lead contact upon request. Additional Supplemental Items are available from Mendeley Data at: https://doi.org/10.17632/5bmb564d8t.1.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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