Reducing cell intrinsic immunity to mRNA vaccine alters adaptive immune responses in mice.
MT: Bioinformatics
RNA vaccine
cell intrinsic
inflammation
influenza
innate
sensing
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
12 Dec 2023
12 Dec 2023
Historique:
medline:
25
10
2023
pubmed:
25
10
2023
entrez:
25
10
2023
Statut:
epublish
Résumé
The response to mRNA vaccines needs to be sufficient for immune cell activation and recruitment, but moderate enough to ensure efficacious antigen expression. The choice of the cap structure and use of N1-methylpseudouridine (m1Ψ) instead of uridine, which have been shown to reduce RNA sensing by the cellular innate immune system, has led to improved efficacy of mRNA vaccine platforms. Understanding how RNA modifications influence the cell intrinsic immune response may help in the development of more effective mRNA vaccines. In the current study, we compared mRNA vaccines in mice against influenza virus using three different mRNA formats: uridine-containing mRNA (D1-uRNA), m1Ψ-modified mRNA (D1-modRNA), and D1-modRNA with a cap1 structure (cC1-modRNA). D1-uRNA vaccine induced a significantly different gene expression profile to the modified mRNA vaccines, with an up-regulation of
Identifiants
pubmed: 37876532
doi: 10.1016/j.omtn.2023.102045
pii: S2162-2531(23)00263-9
pmc: PMC10591005
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102045Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
E.J.J., S.K., J.M., L.A.S., A.B.V., K.K., U.S., and S.E. are employees at BioNTech SE (Mainz, Germany). U.S. is cofounder and management board member of BioNTech SE (Mainz, Germany). A.B.V., K.K., U.S., and S.E. are inventors on patents and patent applications related to RNA technology. A.B.V., K.K., U.S., and S.E. hold securities from BioNTech SE.
Références
Immunity. 2005 Aug;23(2):165-75
pubmed: 16111635
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Nat Rev Immunol. 2021 Oct;21(10):626-636
pubmed: 34373623
Lancet Infect Dis. 2022 Mar;22(3):329-340
pubmed: 34826381
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Nature. 2001 Oct 18;413(6857):732-8
pubmed: 11607032
Front Immunol. 2022 Oct 14;13:983000
pubmed: 36311701
Immunity. 2020 Oct 13;53(4):724-732.e7
pubmed: 32783919
Adv Immunol. 2009;101:191-236
pubmed: 19231596
Clin Exp Immunol. 2020 Nov;202(2):162-192
pubmed: 32935331
Front Immunol. 2014 Jul 10;5:316
pubmed: 25071777
Nature. 2021 Apr;592(7853):283-289
pubmed: 33524990
Immunology. 2017 Aug;151(4):451-463
pubmed: 28375554
Front Immunol. 2018 Jan 31;9:126
pubmed: 29445377
Mol Ther. 2008 Nov;16(11):1833-40
pubmed: 18797453
Cell Rep. 2021 Aug 10;36(6):109504
pubmed: 34352226
Nat Rev Immunol. 2016 Sep;16(9):566-80
pubmed: 27455396
Mol Ther Nucleic Acids. 2019 Apr 15;15:26-35
pubmed: 30933724
Biomaterials. 2016 Dec;109:78-87
pubmed: 27680591
Mol Ther. 2019 Apr 10;27(4):824-836
pubmed: 30638957
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Clin Exp Immunol. 2019 Feb;195(2):139-152
pubmed: 30422307
J Virol. 2019 Mar 5;93(6):
pubmed: 30567988
NPJ Vaccines. 2017 Oct 19;2:29
pubmed: 29263884
Nat Commun. 2018 Aug 22;9(1):3361
pubmed: 30135514
IUBMB Life. 2006 Sep;58(9):508-14
pubmed: 17002978
Gene Ther. 2010 Aug;17(8):961-71
pubmed: 20410931
Nature. 2021 Aug;596(7872):410-416
pubmed: 34252919
Immunity. 2021 Dec 14;54(12):2877-2892.e7
pubmed: 34852217
NPJ Vaccines. 2021 Apr 16;6(1):57
pubmed: 33863911
Curr Top Microbiol Immunol. 2022;440:31-70
pubmed: 33861374
Mol Ther. 2017 Dec 6;25(12):2635-2647
pubmed: 28958578
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Nucleic Acids Res. 2016 Sep 19;44(16):7511-26
pubmed: 27317694
Appl Microbiol Biotechnol. 2006 Dec;73(3):495-504
pubmed: 17063328
Vaccine. 2011 Feb 17;29(9):1812-23
pubmed: 21215831
Nat Immunol. 2014 Feb;15(2):195-204
pubmed: 24336226
Sci Transl Med. 2021 Sep 08;13(610):eabc7804
pubmed: 34516826
RNA. 2004 Sep;10(9):1479-87
pubmed: 15317978
RNA. 2001 Oct;7(10):1486-95
pubmed: 11680853
Nucleic Acids Res. 2011 Nov;39(21):9329-38
pubmed: 21813458
Immunity. 2008 Jul 18;29(1):150-64
pubmed: 18631455
Methods Mol Biol. 2013;969:55-72
pubmed: 23296927
J Exp Med. 2018 Jun 4;215(6):1571-1588
pubmed: 29739835
Blood. 2006 Dec 15;108(13):4009-17
pubmed: 16940422
Genes Dis. 2015 Mar;2(1):46-56
pubmed: 25815367
PLoS One. 2016 May 10;11(5):e0154656
pubmed: 27164006
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
NPJ Vaccines. 2022 Aug 1;7(1):88
pubmed: 35915094
BMC Bioinformatics. 2019 Jun 13;20(1):331
pubmed: 31195976
Annu Rev Virol. 2019 Sep 29;6(1):567-584
pubmed: 31283436
Nature. 2017 Mar 9;543(7644):248-251
pubmed: 28151488
Eur J Immunol. 2012 Feb;42(2):353-63
pubmed: 22057556
Science. 2021 Jan 8;371(6525):145-153
pubmed: 33414215
Front Immunol. 2020 Jul 09;11:1259
pubmed: 32733442
Cell. 1978 Mar;13(3):565-72
pubmed: 657268
J Transl Med. 2017 Jan 3;15(1):1
pubmed: 28049494
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
Immunology. 2022 Mar;165(3):301-311
pubmed: 34775601
Nature. 2021 Jul;595(7868):572-577
pubmed: 34044428
Cell. 1993 Mar 12;72(5):753-65
pubmed: 7680958