A third dose of the unmodified COVID-19 mRNA vaccine CVnCoV enhances quality and quantity of immune responses.
COVID-19
SARS-CoV-2
affinity maturation
antibody response
innate immunity
mRNA vaccine
vaccine
vaccine biodistribution
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:
08 Dec 2022
08 Dec 2022
Historique:
received:
04
08
2022
accepted:
04
10
2022
pubmed:
12
10
2022
medline:
12
10
2022
entrez:
11
10
2022
Statut:
ppublish
Résumé
A third vaccine dose is often required to achieve potent, long-lasting immune responses. We investigated the effect of three 8-μg doses of CVnCoV, CureVac's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate containing sequence-optimized unmodified mRNA encoding the spike (S) glycoprotein, administered at 0, 4, and 28 weeks, on immune responses in rhesus macaques. After the third dose, S-specific binding and neutralizing antibodies increased 50-fold compared with post-dose 2 levels, with increased responses also evident in the lower airways and against the SARS-CoV-2 B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) variants. Enhanced binding affinity of serum antibodies after the third dose correlated with higher somatic hypermutation in S-specific B cells, corresponding with improved binding properties of monoclonal antibodies expressed from isolated B cells. Administration of low-dose mRNA led to fewer cells expressing antigen
Identifiants
pubmed: 36217434
doi: 10.1016/j.omtm.2022.10.001
pii: S2329-0501(22)00143-7
pmc: PMC9535876
doi:
Types de publication
Journal Article
Langues
eng
Pagination
309-323Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
S.O.M., E.J., K.S., S.R., and B.P. are employees of CureVac AG.
Références
Cell. 2021 Aug 5;184(16):4203-4219.e32
pubmed: 34242577
Cell. 2022 Jan 6;185(1):113-130.e15
pubmed: 34921774
Vaccines (Basel). 2021 Jan 18;9(1):
pubmed: 33477534
Cell. 2021 Apr 15;184(8):2183-2200.e22
pubmed: 33756110
Science. 2020 May 8;368(6491):630-633
pubmed: 32245784
Lancet. 2017 Sep 23;390(10101):1511-1520
pubmed: 28754494
Front Immunol. 2016 Nov 21;7:512
pubmed: 27917174
Cell Rep. 2022 Feb 15;38(7):110368
pubmed: 35123652
Blood. 2012 Mar 1;119(9):2044-55
pubmed: 22246032
Immunity. 2021 Feb 9;54(2):355-366.e4
pubmed: 33484642
JCI Insight. 2018 May 17;3(10):
pubmed: 29769448
Nat Med. 2021 Nov;27(11):2032-2040
pubmed: 34588689
Nature. 2022 Jan;601(7893):410-414
pubmed: 34794169
N Engl J Med. 2021 Oct 21;385(17):1627-1629
pubmed: 34525276
Nature. 2020 Aug;584(7821):437-442
pubmed: 32555388
Science. 2021 Dec 03;374(6572):abm0829
pubmed: 34648302
JCI Insight. 2021 Nov 22;6(22):
pubmed: 34665783
Lancet. 2021 Dec 18;398(10318):2258-2276
pubmed: 34863358
Vaccine X. 2022 Aug;11:100189
pubmed: 35791320
N Engl J Med. 2020 Oct 15;383(16):1544-1555
pubmed: 32722908
Vaccine. 2009 May 18;27(23):3045-52
pubmed: 19428918
Nature. 2020 Jul;583(7815):290-295
pubmed: 32422645
Nat Biomed Eng. 2019 May;3(5):371-380
pubmed: 30936432
Nat Rev Microbiol. 2021 Jul;19(7):409-424
pubmed: 34075212
J Exp Med. 2020 Feb 3;217(2):
pubmed: 31704807
Sci Transl Med. 2017 Jun 7;9(393):
pubmed: 28592561
Cell Rep. 2021 Aug 10;36(6):109504
pubmed: 34352226
mSphere. 2020 Sep 16;5(5):
pubmed: 32938700
Cell Rep. 2020 Mar 24;30(12):3964-3971.e7
pubmed: 32209459
Nature. 2020 Oct;586(7830):594-599
pubmed: 32998157
Front Immunol. 2019 Apr 02;10:614
pubmed: 31001251
Cell. 2022 Mar 17;185(6):1025-1040.e14
pubmed: 35148837
J Immunol Methods. 2012 Dec 14;386(1-2):85-93
pubmed: 22989932
Nat Med. 2022 Mar;28(3):496-503
pubmed: 35090165
Lancet Infect Dis. 2022 Mar;22(3):329-340
pubmed: 34826381
Nat Commun. 2015 Apr 10;6:6565
pubmed: 25858157
J Exp Med. 2003 Jul 21;198(2):281-91
pubmed: 12874261
Cell. 2021 Jul 22;184(15):3936-3948.e10
pubmed: 34192529
Nature. 2021 Aug;596(7872):410-416
pubmed: 34252919
Viruses. 2021 Aug 19;13(8):
pubmed: 34452509
Cell. 2022 Mar 17;185(6):1008-1024.e15
pubmed: 35202565
J Biol Chem. 2001 Aug 3;276(31):29188-94
pubmed: 11387331
Immunity. 2021 Sep 14;54(9):2005-2023.e10
pubmed: 34525339
Cell Host Microbe. 2014 Jul 9;16(1):115-27
pubmed: 24981333
Front Immunol. 2022 Jan 14;12:808932
pubmed: 35095897
Mol Ther. 2017 Dec 6;25(12):2635-2647
pubmed: 28958578
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Vaccine. 2010 Oct 21;28(45):7256-66
pubmed: 20846528
Science. 2020 Jun 12;368(6496):1274-1278
pubmed: 32404477
Science. 2020 Nov 20;370(6519):950-957
pubmed: 32972994
Science. 2021 Jun 4;372(6546):1108-1112
pubmed: 33947773
Nat Med. 2021 Jul;27(7):1205-1211
pubmed: 34002089
J Leukoc Biol. 2011 Jun;89(6):811-21
pubmed: 21233412
Science. 2021 Sep 17;373(6561):eabj0299
pubmed: 34529476
Nat Commun. 2016 Dec 20;7:13642
pubmed: 27995928
Cell. 2022 Feb 3;185(3):457-466.e4
pubmed: 34995482
Nature. 2022 Apr;604(7904):141-145
pubmed: 35168246
J Med Virol. 2020 Oct;92(10):2096-2104
pubmed: 32383254
Vaccine. 2021 Feb 22;39(8):1310-1318
pubmed: 33487468
Nature. 2021 Apr;592(7853):283-289
pubmed: 33524990
Lancet Microbe. 2022 Jan;3(1):e52-e61
pubmed: 34806056
Nat Rev Immunol. 2017 Jun;17(6):349-362
pubmed: 28436425
Wien Klin Wochenschr. 2021 Sep;133(17-18):931-941
pubmed: 34378087
Nat Protoc. 2021 Jun;16(6):3114-3140
pubmed: 33893470
Science. 2020 Aug 7;369(6504):643-650
pubmed: 32540902
Vaccines (Basel). 2022 Mar 25;10(4):
pubmed: 35455257
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
Immunity. 2001 Apr;14(4):461-70
pubmed: 11336691
N Engl J Med. 2021 Jan 7;384(1):80-82
pubmed: 33270381
Cell. 2021 Apr 29;184(9):2332-2347.e16
pubmed: 33761326
Cell. 2022 May 26;185(11):1875-1887.e8
pubmed: 35523182