Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
19 Jun 2023
19 Jun 2023
Historique:
pubmed:
30
8
2022
medline:
30
8
2022
entrez:
29
8
2022
Statut:
epublish
Résumé
Multivalent antigen display is a well-established principle to enhance humoral immunity. Protein-based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control valency on fixed scaffold geometries and are thymus-dependent antigens that elicit neutralizing B cell memory themselves, which can distract immune responses. Here, we investigated DNA origami as an alternative material for multivalent antigen display in vivo, applied to the receptor binding domain (RBD) of SARS-CoV2 that is the primary antigenic target of neutralizing antibody responses. Icosahedral DNA-VLPs elicited neutralizing antibodies to SARS-CoV-2 in a valency-dependent manner following sequential immunization in mice, quantified by pseudo- and live-virus neutralization assays. Further, induction of B cell memory against the RBD required T cell help, but the immune sera did not contain boosted, class-switched antibodies against the DNA scaffold. This contrasted with protein-based VLP display of the RBD that elicited B cell memory against both the target antigen and the scaffold. Thus, DNA-based VLPs enhance target antigen immunogenicity without generating off-target, scaffold-directed immune memory, thereby offering a potentially important alternative material for particulate vaccine design.
Identifiants
pubmed: 36032975
doi: 10.1101/2022.08.16.504128
pmc: PMC9413718
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI153098
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007245
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI160908
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI146779
Pays : United States
Organisme : NIDA NIH HHS
ID : DP2 DA040254
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008313
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124378
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI060354
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155447
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB026008
Pays : United States
Déclaration de conflit d'intérêts
Competing interests The Massachusetts Institute of Technology has filed a patent (US application number 16/752,394) covering the use of DNA origami as a vaccine platform on behalf of the co-inventors (E.-C. W. and M. B.).
Références
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Immunity. 2017 May 16;46(5):804-817.e7
pubmed: 28514687
N Engl J Med. 2021 Sep 23;385(13):1172-1183
pubmed: 34192426
Nature. 2001 May 24;411(6836):489-94
pubmed: 11373683
Small. 2022 Jul;18(26):e2108063
pubmed: 35633287
Cell Rep Med. 2022 Oct 18;3(10):100780
pubmed: 36206752
J Immunol. 2008 May 1;180(9):5816-25
pubmed: 18424700
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021 Jan;13(1):e1657
pubmed: 32672007
Front Immunol. 2021 Sep 09;12:730471
pubmed: 34566992
Nucleic Acids Res. 2021 Oct 11;49(18):10265-10274
pubmed: 34508356
Proc Natl Acad Sci U S A. 2021 Sep 21;118(38):
pubmed: 34493582
Nat Nanotechnol. 2020 Aug;15(8):716-723
pubmed: 32601450
Nature. 2022 Sep;609(7929):998-1004
pubmed: 36131022
Nat Nanotechnol. 2019 Feb;14(2):184-190
pubmed: 30643273
Annu Rev Biophys. 2019 May 6;48:395-419
pubmed: 31084582
Nature. 1984 Mar 29-Apr 4;308(5958):457-60
pubmed: 6709052
Nat Mater. 2021 Mar;20(3):421-430
pubmed: 32895504
Science. 2022 Aug 5;377(6606):eabq0839
pubmed: 35857620
ACS Nano. 2022 Dec 27;16(12):20340-20352
pubmed: 36459697
Trends Immunol. 2021 Nov;42(11):956-959
pubmed: 34580004
Science. 2013 May 10;340(6133):711-6
pubmed: 23539181
Annu Rev Immunol. 2019 Apr 26;37:97-123
pubmed: 31026412
Nat Rev Immunol. 2009 Jan;9(1):15-27
pubmed: 19079135
Cell. 2020 Nov 25;183(5):1367-1382.e17
pubmed: 33160446
Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):E6639-E6648
pubmed: 27702895
J Infect Dis. 2017 Jun 15;215(12):1782-1788
pubmed: 28398521
Nature. 1992 Nov 19;360(6401):225-31
pubmed: 1359428
Proc Natl Acad Sci U S A. 2021 Sep 21;118(38):
pubmed: 34470866
Immunity. 2020 Sep 15;53(3):548-563.e8
pubmed: 32857950
mBio. 2019 Feb 26;10(1):
pubmed: 30808695
Methods Enzymol. 2003;373:74-91
pubmed: 14714397
Sci Adv. 2021 Mar 19;7(12):
pubmed: 33741598
Science. 2021 Feb 12;371(6530):735-741
pubmed: 33436524
Annu Rev Immunol. 2022 Apr 26;40:413-442
pubmed: 35113731
Cell. 2021 Jan 21;184(2):476-488.e11
pubmed: 33412089
Nat Protoc. 2016 Feb;11(2):193-213
pubmed: 26741406
Nature. 2014 Mar 13;507(7491):201-6
pubmed: 24499818
Mol Ther. 2016 Feb;24(1):6-16
pubmed: 26478249
Nano Lett. 2012 Aug 8;12(8):4254-9
pubmed: 22746330
Nature. 2021 Jun;594(7862):253-258
pubmed: 33873199
Nat Rev Bioeng. 2023 Feb;1(2):107-124
pubmed: 37772035
Science. 2023 Jan 27;379(6630):eabn8934
pubmed: 36701450
NPJ Vaccines. 2021 May 13;6(1):70
pubmed: 33986287
ACS Nano. 2022 Jun 28;16(6):8954-8966
pubmed: 35640255
Nat Rev Immunol. 2013 Feb;13(2):118-32
pubmed: 23348416
Cell Rep. 2021 Dec 21;37(12):110143
pubmed: 34919799
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1080-5
pubmed: 22247289
Cell. 2019 Mar 7;176(6):1420-1431.e17
pubmed: 30849373
Science. 2019 Dec 6;366(6470):
pubmed: 31806786
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):E3503-12
pubmed: 23151505
Nat Rev Immunol. 2021 Feb;21(2):73-82
pubmed: 33340022
J Immunol. 1980 Jan;124(1):202-6
pubmed: 6965290
Nat Rev Mater. 2023 Feb;8(2):123-138
pubmed: 37206669
Science. 2020 May 8;368(6491):630-633
pubmed: 32245784
Nat Rev Chem. 2021;5(4):225-239
pubmed: 33585701
Science. 2016 Jun 24;352(6293):1534
pubmed: 27229143
Nature. 1980 Jun 26;285(5767):664-7
pubmed: 6967189
Nano Lett. 2019 Oct 9;19(10):7226-7235
pubmed: 31508968
Nature. 2006 Mar 16;440(7082):297-302
pubmed: 16541064
Science. 2020 Jun 12;368(6496):1274-1278
pubmed: 32404477
Cell. 2019 Apr 18;177(3):524-540
pubmed: 31002794
Cell Rep. 2022 Mar 22;38(12):110561
pubmed: 35303475
Elife. 2020 Apr 02;9:
pubmed: 32228860
Nature. 2012 Sep 27;489(7417):566-70
pubmed: 22932267
Nat Immunol. 2019 Mar;20(3):362-372
pubmed: 30742080
Science. 2019 Feb 8;363(6427):649-654
pubmed: 30573546
Nat Nanotechnol. 2021 Jan;16(1):16-24
pubmed: 33199883
Nat Med. 2015 Sep;21(9):1065-70
pubmed: 26301691
Nature. 2023 Mar;615(7952):482-489
pubmed: 36646114
Elife. 2019 Jan 17;8:
pubmed: 30648968
Immunity. 2018 Jan 16;48(1):133-146.e6
pubmed: 29287996
Sci Transl Med. 2018 Aug 29;10(456):
pubmed: 30158151
Nature. 2021 Apr;592(7855):623-628
pubmed: 33762730
Bioconjug Chem. 2022 Nov 16;33(11):2018-2034
pubmed: 35487503
Cell. 2021 Apr 29;184(9):2523
pubmed: 33930298
Nat Immunol. 2013 Feb;14(2):119-26
pubmed: 23334833
Nano Lett. 2022 Mar 23;22(6):2506-2513
pubmed: 35266392
J Exp Med. 2013 Apr 8;210(4):655-63
pubmed: 23530120
Cell. 2015 Aug 27;162(5):1090-100
pubmed: 26279189
Nat Med. 2010 Mar;16(3):334-8
pubmed: 20111039
Cell Rep Med. 2022 Dec 20;3(12):100834
pubmed: 36423634
Sci Transl Med. 2017 Mar 8;9(380):
pubmed: 28275152
Immunity. 2019 Oct 15;51(4):735-749.e8
pubmed: 31563464
Science. 2015 Jul 10;349(6244):156-61
pubmed: 26089355
Immunity. 2019 May 21;50(5):1132-1148
pubmed: 31117010
Proc Natl Acad Sci U S A. 1976 Oct;73(10):3671-5
pubmed: 62364
Nature. 2013 Jul 4;499(7456):102-6
pubmed: 23698367
NPJ Vaccines. 2021 Oct 28;6(1):128
pubmed: 34711846
Nat Immunol. 2019 Aug;20(8):963-969
pubmed: 31285625
Nat Commun. 2021 Jan 14;12(1):372
pubmed: 33446655
Curr Opin Immunol. 2020 Aug;65:1-6
pubmed: 32200132
J Exp Med. 2006 Feb 20;203(2):305-10
pubmed: 16476769
ACS Nano. 2021 Sep 28;15(9):14316-14322
pubmed: 34490781
J Mol Biol. 2008 Jun 27;380(1):252-63
pubmed: 18508079