COVID-19 adenovirus vector vaccine induces higher interferon and pro-inflammatory responses than mRNA vaccines in human PBMCs, macrophages and moDCs.
Humans
Interferons
/ metabolism
Leukocytes, Mononuclear
COVID-19 Vaccines
ChAdOx1 nCoV-19
Tumor Necrosis Factor-alpha
/ metabolism
mRNA Vaccines
BNT162 Vaccine
2019-nCoV Vaccine mRNA-1273
Interleukin-2
/ metabolism
Interleukin-6
/ metabolism
Pandemics
Dendritic Cells
COVID-19
Cytokines
/ metabolism
Macrophages
Vaccines
RNA, Messenger
/ metabolism
Adenoviridae
A549 cells
Adenovirus vector vaccine
COVID-19
Human PBMC
IFN response
Macrophage
Pro-inflammatory cytokines
mRNA vaccine
moDC
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
13 06 2023
13 06 2023
Historique:
received:
09
03
2022
revised:
05
04
2023
accepted:
18
04
2023
medline:
14
6
2023
pubmed:
5
5
2023
entrez:
4
5
2023
Statut:
ppublish
Résumé
During the COVID-19 pandemic multiple vaccines were rapidly developed and widely used throughout the world. At present there is very little information on COVID-19 vaccine interactions with primary human immune cells such as peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages and dendritic cells (moDCs). Human PBMCs, macrophages and moDCs were stimulated with different COVID-19 vaccines, and the expression of interferon (IFN-λ1, IFN-α1), pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, CXCL-4, CXCL-10, TNF-α) and Th1-type cytokine mRNAs (IL-2, IFN-γ) were analyzed by qPCR. In addition, the expression of vaccine induced spike (S) protein and antiviral molecules were studied in primary immune cells and in A549 lung epithelial cells. Adenovirus vector (Ad-vector) vaccine AZD1222 induced high levels of IFN-λ1, IFN-α1, CXCL-10, IL-6, and TNF-α mRNAs in PBMCs at early time points of stimulation while the expression of IFN-γ and IL-2 mRNA took place at later times. AZD1222 also induced IFN-λ1, CXCL-10 and IL-6 mRNA expression in monocyte-derived macrophages and DCs in a dose-dependent fashion. AZD1222 also activated the phosphorylation of IRF3 and induced MxA expression. BNT162b2 and mRNA-1273 mRNA vaccines failed to induce or induced very weak cytokine gene expression in all cell models. None of the vaccines enhanced the expression of CXCL-4. AZD1222 and mRNA-1273 vaccines induced high expression of S protein in all studied cells. Ad-vector vaccine induces higher IFN and pro-inflammatory responses than the mRNA vaccines in human immune cells. This data shows that AZD1222 readily activates IFN and pro-inflammatory cytokine gene expression in PBMCs, macrophages and DCs, but fails to further enhance CXCL-4 mRNA expression.
Sections du résumé
BACKGROUND
During the COVID-19 pandemic multiple vaccines were rapidly developed and widely used throughout the world. At present there is very little information on COVID-19 vaccine interactions with primary human immune cells such as peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages and dendritic cells (moDCs).
METHODS
Human PBMCs, macrophages and moDCs were stimulated with different COVID-19 vaccines, and the expression of interferon (IFN-λ1, IFN-α1), pro-inflammatory (IL-1β, IL-6, IL-8, IL-18, CXCL-4, CXCL-10, TNF-α) and Th1-type cytokine mRNAs (IL-2, IFN-γ) were analyzed by qPCR. In addition, the expression of vaccine induced spike (S) protein and antiviral molecules were studied in primary immune cells and in A549 lung epithelial cells.
RESULTS
Adenovirus vector (Ad-vector) vaccine AZD1222 induced high levels of IFN-λ1, IFN-α1, CXCL-10, IL-6, and TNF-α mRNAs in PBMCs at early time points of stimulation while the expression of IFN-γ and IL-2 mRNA took place at later times. AZD1222 also induced IFN-λ1, CXCL-10 and IL-6 mRNA expression in monocyte-derived macrophages and DCs in a dose-dependent fashion. AZD1222 also activated the phosphorylation of IRF3 and induced MxA expression. BNT162b2 and mRNA-1273 mRNA vaccines failed to induce or induced very weak cytokine gene expression in all cell models. None of the vaccines enhanced the expression of CXCL-4. AZD1222 and mRNA-1273 vaccines induced high expression of S protein in all studied cells.
CONCLUSIONS
Ad-vector vaccine induces higher IFN and pro-inflammatory responses than the mRNA vaccines in human immune cells. This data shows that AZD1222 readily activates IFN and pro-inflammatory cytokine gene expression in PBMCs, macrophages and DCs, but fails to further enhance CXCL-4 mRNA expression.
Identifiants
pubmed: 37142461
pii: S0264-410X(23)00463-2
doi: 10.1016/j.vaccine.2023.04.049
pmc: PMC10126225
pii:
doi:
Substances chimiques
Interferons
9008-11-1
COVID-19 Vaccines
0
ChAdOx1 nCoV-19
B5S3K2V0G8
Tumor Necrosis Factor-alpha
0
mRNA Vaccines
0
BNT162 Vaccine
0
2019-nCoV Vaccine mRNA-1273
EPK39PL4R4
Interleukin-2
0
Interleukin-6
0
Cytokines
0
Vaccines
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3813-3823Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
J Infect Dis. 2021 Jul 15;224(2):218-228
pubmed: 33905505
N Engl J Med. 2007 Mar 1;356(9):891-3
pubmed: 17329695
Nature. 2021 Sep;597(7876):318-324
pubmed: 34522017
J Immunol. 1993 Mar 1;150(5):1715-26
pubmed: 7679692
Viruses. 2021 Feb 09;13(2):
pubmed: 33572452
Front Immunol. 2020 May 19;11:909
pubmed: 32508823
ACS Cent Sci. 2021 Apr 28;7(4):594-602
pubmed: 34056089
J Hematol Oncol. 2020 Sep 4;13(1):120
pubmed: 32887634
Circulation. 2021 Aug 10;144(6):471-484
pubmed: 34281357
Front Public Health. 2020 Jul 03;8:281
pubmed: 32733837
NPJ Vaccines. 2020 Sep 28;5:91
pubmed: 33083026
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
Vaccine. 2021 Jan 15;39(3):457-459
pubmed: 33339671
J Mol Biol. 2022 Mar 30;434(6):167280
pubmed: 34606831
Curr Opin HIV AIDS. 2010 Sep;5(5):386-90
pubmed: 20978378
J Virol. 2005 Aug;79(15):9608-17
pubmed: 16014923
NPJ Vaccines. 2021 Aug 16;6(1):104
pubmed: 34400651
NPJ Vaccines. 2021 Aug 5;6(1):97
pubmed: 34354082
Blood. 2021 Dec 2;138(22):2256-2268
pubmed: 34587242
Microbiol Spectr. 2021 Sep 3;9(1):e0077421
pubmed: 34378952
PLoS One. 2021 Sep 8;16(9):e0256980
pubmed: 34495988
Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1663-1669
pubmed: 33629336
Vaccines (Basel). 2021 Jan 18;9(1):
pubmed: 33477534
Patient Saf Surg. 2021 May 1;15(1):20
pubmed: 33933145
RNA Biol. 2012 Nov;9(11):1319-30
pubmed: 23064118
Nat Commun. 2021 Oct 6;12(1):5861
pubmed: 34615860
Vaccines (Basel). 2018 May 24;6(2):
pubmed: 29794983
Paediatr Respir Rev. 2020 Sep;35:43-49
pubmed: 32653463
ACS Cent Sci. 2021 May 26;7(5):748-756
pubmed: 34075344
Hum Gene Ther. 1998 Aug 10;9(12):1769-74
pubmed: 9721087
Cureus. 2021 Mar 25;13(3):e14099
pubmed: 33786251
N Engl J Med. 2021 Jun 10;384(23):2202-2211
pubmed: 33861525
Thromb Res. 2021 Dec;208:129-137
pubmed: 34768097
J Leukoc Biol. 2007 Sep;82(3):710-20
pubmed: 17595377
Eur J Case Rep Intern Med. 2021 Jun 14;8(7):002681
pubmed: 34268277
J Postgrad Med. 2016 Jan-Mar;62(1):4-11
pubmed: 26732191
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Indian J Clin Biochem. 2021 Oct;36(4):427-439
pubmed: 33814753
N Engl J Med. 2021 Jul 15;385(3):e11
pubmed: 34133853
Nat Rev Immunol. 2021 Apr;21(4):195-197
pubmed: 33674759
Sci Adv. 2021 Dec 03;7(49):eabl8213
pubmed: 34851659
Biomark Res. 2014 Jan 07;2(1):1
pubmed: 24398220
Am J Emerg Med. 2021 Nov;49:58-61
pubmed: 34062319
N Engl J Med. 2021 Jun 3;384(22):2124-2130
pubmed: 33835768
Lancet. 2017 Feb 11;389(10069):621-628
pubmed: 28017399
J Leukoc Biol. 2004 May;75(5):764-71
pubmed: 14966192
BMC Med. 2022 Jan 14;20(1):26
pubmed: 35027067
Clin Immunol. 2021 Jan;222:108634
pubmed: 33217545
Am J Respir Crit Care Med. 2017 May 1;195(9):1171-1180
pubmed: 28060545