Differential T cell immune responses to deamidated adeno-associated virus vector.
T cell epitopes
adeno-associated virus vector
deamidation
gene therapy
immunogenicity
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
10 Mar 2022
10 Mar 2022
Historique:
received:
03
11
2021
accepted:
16
01
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
26
2
2022
Statut:
epublish
Résumé
Despite the high safety profile demonstrated in clinical trials, the immunogenicity of adeno-associated virus (AAV)-mediated gene therapy remains a major hurdle. Specifically, T-cell-mediated immune responses to AAV vectors are related to loss of efficacy and potential liver toxicities. As post-translational modifications in T cell epitopes have the potential to affect immune reactions, the cellular immune responses to peptides derived from spontaneously deamidated AAV were investigated. Here, we report that highly deamidated sites in AAV9 contain CD4 T cell epitopes with a Th1 cytokine pattern in multiple human donors with diverse human leukocyte antigen (HLA) backgrounds. Furthermore, some peripheral blood mononuclear cell (PBMC) samples demonstrated differential T cell activation to deamidated or non-deamidated epitopes. Also,
Identifiants
pubmed: 35211638
doi: 10.1016/j.omtm.2022.01.005
pii: S2329-0501(22)00006-7
pmc: PMC8829777
doi:
Types de publication
Journal Article
Langues
eng
Pagination
255-267Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
Clin Vaccine Immunol. 2016 May 06;23(5):396-402
pubmed: 26912784
BMC Bioinformatics. 2010 Nov 22;11:568
pubmed: 21092157
J Biol Chem. 2005 May 6;280(18):18498-503
pubmed: 15749706
Methods Mol Biol. 2019;1950:51-83
pubmed: 30783968
J Exp Med. 2001 Oct 15;194(8):1165-70
pubmed: 11602644
Front Immunol. 2018 Jun 14;9:1369
pubmed: 29963059
Mol Ther Methods Clin Dev. 2015 Sep 30;2:15029
pubmed: 26445723
Pharm Res. 2004 Jun;21(6):897-903
pubmed: 15212151
Front Immunol. 2017 Feb 23;8:194
pubmed: 28280496
Mol Ther. 2020 Mar 4;28(3):709-722
pubmed: 31968213
J Virol. 1988 Aug;62(8):2745-54
pubmed: 2839699
AAPS J. 2017 Jan;19(1):117-129
pubmed: 27796910
Annu Rev Immunol. 2006;24:419-66
pubmed: 16551255
Sci Immunol. 2021 Apr 14;6(58):
pubmed: 33853928
J Biol Chem. 1993 Dec 15;268(35):26279-85
pubmed: 8253750
Nat Med. 2007 Apr;13(4):419-22
pubmed: 17369837
J Biol Chem. 1999 Aug 6;274(32):22321-7
pubmed: 10428801
Nat Protoc. 2006;1(3):1412-28
pubmed: 17406430
J Infect Dis. 2009 Feb 1;199(3):381-90
pubmed: 19133809
Immunogenetics. 2011 Jun;63(6):325-35
pubmed: 21305276
Hum Gene Ther. 2006 Apr;17(4):440-7
pubmed: 16610931
Front Oncol. 2019 Apr 24;9:297
pubmed: 31069169
Hum Gene Ther. 2010 Jun;21(6):704-12
pubmed: 20095819
Hum Gene Ther. 2017 Nov;28(11):1061-1074
pubmed: 28835127
Mol Ther. 2018 Dec 5;26(12):2848-2862
pubmed: 30343890
J Exp Med. 2000 Feb 21;191(4):603-12
pubmed: 10684852
Hum Gene Ther. 2020 Apr;31(7-8):398-399
pubmed: 32302233
Annu Rev Immunol. 2020 Apr 26;38:123-145
pubmed: 32045313
Mol Ther Methods Clin Dev. 2020 Oct 10;19:387-397
pubmed: 33209964
J Immunol. 1996 Aug 1;157(3):1000-5
pubmed: 8757603
PLoS One. 2019 Oct 16;14(10):e0223899
pubmed: 31618250
Nucleic Acids Res. 2020 Jul 2;48(W1):W449-W454
pubmed: 32406916
Front Immunol. 2021 Feb 09;11:629399
pubmed: 33633747
J Immunol. 2012 Jun 15;188(12):6418-24
pubmed: 22593612
J Clin Invest. 2009 Jun;119(6):1688-95
pubmed: 19436115
Mol Ther Methods Clin Dev. 2020 May 22;18:98-118
pubmed: 32995354
Front Immunol. 2021 Mar 11;12:637963
pubmed: 33777029
J Pharm Sci. 2006 Nov;95(11):2321-36
pubmed: 16960822
J Mol Med (Berl). 2009 Nov;87(11):1045-51
pubmed: 19763524
Blood. 2021 Feb 11;137(6):763-774
pubmed: 33067633
N Engl J Med. 2011 Dec 22;365(25):2357-65
pubmed: 22149959
J Immunol. 2017 Nov 1;199(9):3360-3368
pubmed: 28978689
Mol Ther. 2011 Nov;19(11):2021-30
pubmed: 21587208
Nucleic Acids Res. 2020 Jan 8;48(D1):D783-D788
pubmed: 31722398
Electrophoresis. 2010 Jun;31(11):1764-72
pubmed: 20446295
Biochem Biophys Res Commun. 2009 Jan 16;378(3):433-8
pubmed: 19028452
J Gen Virol. 2009 Nov;90(Pt 11):2622-2633
pubmed: 19641045
Front Immunol. 2020 Apr 17;11:670
pubmed: 32362898
J Exp Med. 2001 Jun 4;193(11):1239-46
pubmed: 11390431
Annu Rev Immunol. 2004;22:745-63
pubmed: 15032595
Gene Ther. 1999 Jun;6(6):973-85
pubmed: 10455399
Gene Ther. 2022 Feb;29(1-2):41-54
pubmed: 33432123
Nat Med. 2006 Mar;12(3):342-7
pubmed: 16474400
Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2046-53
pubmed: 23580623