B cell-derived cfDNA after primary BNT162b2 mRNA vaccination anticipates memory B cells and SARS-CoV-2 neutralizing antibodies.
BNT162b2
DNA methylation
SARS-CoV-2
Translation to patients
cfDNA
liquid biopsy
mRNA vaccine
memory B-cell
neutralizing antibody
tissue dynamics
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
08 07 2022
08 07 2022
Historique:
received:
14
10
2021
revised:
17
02
2022
accepted:
12
05
2022
pubmed:
19
6
2022
medline:
14
7
2022
entrez:
18
6
2022
Statut:
ppublish
Résumé
Much remains unknown regarding the response of the immune system to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination. We employed circulating cell-free DNA (cfDNA) to assess the turnover of specific immune cell types following administration of the Pfizer/BioNTech vaccine. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35716665
pii: S2666-6340(22)00221-5
doi: 10.1016/j.medj.2022.05.005
pmc: PMC9117261
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Cell-Free Nucleic Acids
0
BNT162 Vaccine
N38TVC63NU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
468-480.e5Subventions
Organisme : NIDDK NIH HHS
ID : UC4 DK104216
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK116274
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests I.F.-F., B.G., R.S., and Y.D. have filed patents related to DNA methylation markers.
Références
Trends Genet. 2021 Aug;37(8):758-770
pubmed: 34006390
Nature. 2020 Oct;586(7830):594-599
pubmed: 32998157
Trends Genet. 2016 Jun;32(6):360-371
pubmed: 27129983
Nat Biotechnol. 2021 May;39(5):586-598
pubmed: 33432199
Immunity. 2020 Dec 15;53(6):1281-1295.e5
pubmed: 33296685
Nature. 2021 Aug;596(7871):276-280
pubmed: 34237773
Genome Res. 2019 Mar;29(3):418-427
pubmed: 30808726
N Engl J Med. 2021 Oct 14;385(16):1474-1484
pubmed: 34320281
Lancet Respir Med. 2021 Sep;9(9):999-1009
pubmed: 34224675
Nature. 2021 Aug;596(7872):417-422
pubmed: 34192737
Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41
pubmed: 26460048
Nat Commun. 2018 Apr 24;9(1):1443
pubmed: 29691397
Sci Transl Med. 2018 Aug 1;10(452):
pubmed: 30068569
Nature. 2021 Dec;600(7889):517-522
pubmed: 34619745
Nature. 2021 Sep;597(7875):268-273
pubmed: 34320609
J Virol. 2021 Jun 24;95(14):e0013021
pubmed: 33893170
Nature. 2021 Aug;596(7872):410-416
pubmed: 34252919
Nature. 2021 Aug;596(7870):109-113
pubmed: 34182569
Front Immunol. 2021 Jul 23;12:690534
pubmed: 34367150
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5503-12
pubmed: 26392541
Euro Surveill. 2020 Jun;25(24):
pubmed: 32583766
Nat Microbiol. 2021 Sep;6(9):1140-1149
pubmed: 34290390
Ann Oncol. 2020 Jun;31(6):745-759
pubmed: 33506766
Sci Transl Med. 2014 Jun 18;6(241):241ra77
pubmed: 24944192
Cell. 2016 Jan 14;164(1-2):57-68
pubmed: 26771485
Elife. 2021 Nov 29;10:
pubmed: 34842142
Lancet. 1997 Aug 16;350(9076):485-7
pubmed: 9274585
N Engl J Med. 2014 Feb 27;370(9):799-808
pubmed: 24571752
Ann Oncol. 2020 Mar;31(3):395-403
pubmed: 32067681
PLoS One. 2016 Aug 04;11(8):e0157385
pubmed: 27490698
Nature. 2012 Jul 19;487(7407):320-4
pubmed: 22763444
Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1826-34
pubmed: 26976580
Nat Rev Cancer. 2017 Apr;17(4):223-238
pubmed: 28233803
Nat Commun. 2018 Nov 29;9(1):5068
pubmed: 30498206
Sci Immunol. 2021 Apr 15;6(58):
pubmed: 33858945
Lancet. 2021 May 15;397(10287):1819-1829
pubmed: 33964222
JCI Insight. 2020 Jul 23;5(14):
pubmed: 32573495
Lancet. 2021 Mar 6;397(10277):875-877
pubmed: 33610193
N Engl J Med. 2021 Jul 22;385(4):320-329
pubmed: 34192428