Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection.
RBD
SARS-CoV-2
immune response
single dose
vaccine
vaccinia virus
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
04 05 2022
04 05 2022
Historique:
received:
30
07
2021
revised:
24
09
2021
accepted:
10
10
2021
pubmed:
24
10
2021
medline:
10
5
2022
entrez:
23
10
2021
Statut:
ppublish
Résumé
The coronavirus disease 2019 (COVID-19) pandemic requires the continued development of safe, long-lasting, and efficacious vaccines for preventive responses to major outbreaks around the world, and especially in isolated and developing countries. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we characterize a temperature-stable vaccine candidate (TOH-Vac1) that uses a replication-competent, attenuated vaccinia virus as a vector to express a membrane-tethered spike receptor binding domain (RBD) antigen. We evaluate the effects of dose escalation and administration routes on vaccine safety, efficacy, and immunogenicity in animal models. Our vaccine induces high levels of SARS-CoV-2 neutralizing antibodies and favorable T cell responses, while maintaining an optimal safety profile in mice and cynomolgus macaques. We demonstrate robust immune responses and protective immunity against SARS-CoV-2 variants after only a single dose. Together, these findings support further development of our novel and versatile vaccine platform as an alternative or complementary approach to current vaccines.
Identifiants
pubmed: 34687845
pii: S1525-0016(21)00515-3
doi: 10.1016/j.ymthe.2021.10.008
pmc: PMC8527104
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1885-1896Subventions
Organisme : CIHR
ID : 448323
Pays : Canada
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
J Virol. 2002 Feb;76(3):1309-27
pubmed: 11773406
Nat Immunol. 2021 Jan;22(1):74-85
pubmed: 32999467
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10847-51
pubmed: 1438287
Nat Commun. 2020 Sep 11;11(1):4541
pubmed: 32917884
Oncolytic Virother. 2015 Jan 28;4:25-31
pubmed: 27512667
Nat Commun. 2021 Jan 12;12(1):288
pubmed: 33436577
Lancet. 2021 Feb 20;397(10275):671-681
pubmed: 33545094
Vaccine. 2017 Jun 5;35(25):3347-3353
pubmed: 28487055
Curr Opin Biotechnol. 2007 Dec;18(6):546-56
pubmed: 18063357
AIDS. 2015 Mar 27;29(6):649-58
pubmed: 25849828
Sci Immunol. 2021 Apr 14;6(58):
pubmed: 33853928
J Virol. 2020 Jun 16;94(13):
pubmed: 32546606
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Int J Mol Sci. 2021 Feb 25;22(5):
pubmed: 33668756
J Gen Virol. 2011 Sep;92(Pt 9):1971-1980
pubmed: 21715594
Nature. 2020 Oct;586(7830):578-582
pubmed: 32731258
Lancet. 2021 Jan 9;397(10269):99-111
pubmed: 33306989
Sci Rep. 2018 Apr 24;8(1):6474
pubmed: 29692427
Sci Rep. 2020 Dec 11;10(1):21779
pubmed: 33311634
J Virol. 2005 Mar;79(5):2678-88
pubmed: 15708987
Nature. 2021 May;593(7857):142-146
pubmed: 33780970
Cell Mol Immunol. 2020 Jun;17(6):621-630
pubmed: 32415260
Gynecol Oncol. 2008 Oct;111(1):95-101
pubmed: 18692224
J Virol. 2013 Nov;87(21):11950-4
pubmed: 23986586
Nature. 2020 Oct;586(7830):567-571
pubmed: 32756549
PLoS Pathog. 2021 Feb 8;17(2):e1009282
pubmed: 33556147
Sci Immunol. 2020 Jun 11;5(48):
pubmed: 32527802
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4512-7
pubmed: 10200293
J Virol. 2000 Aug;74(16):7651-5
pubmed: 10906221
Virol Sin. 2021 Jun;36(3):365-372
pubmed: 32696399
Vaccine. 2018 Aug 16;36(34):5194-5203
pubmed: 30037666
Front Cell Infect Microbiol. 2020 Sep 23;10:581812
pubmed: 33072631
Virology. 2007 Mar 30;360(1):36-49
pubmed: 17098273
J Virol. 2021 Jan 7;:
pubmed: 33414159
Stem Cell Res. 2020 Dec 15;50:102125
pubmed: 33341604
Vaccines (Basel). 2020 Nov 13;8(4):
pubmed: 33202967
Cell Host Microbe. 2020 Sep 9;28(3):475-485.e5
pubmed: 32735849
N Engl J Med. 2021 Jun 10;384(23):2254-2256
pubmed: 33861524
Mol Ther. 2021 Jun 2;29(6):1984-2000
pubmed: 33578036
Immunity. 2021 Mar 9;54(3):542-556.e9
pubmed: 33631118
J Immunol. 2021 Jun 1;206(11):2596-2604
pubmed: 33972374
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Front Immunol. 2019 Dec 18;10:2984
pubmed: 31921215
J Biomed Biotechnol. 2011;2011:970424
pubmed: 21765641
Science. 2020 Oct 2;370(6512):89-94
pubmed: 32753554
Nat Rev Immunol. 2021 Jun;21(6):340-341
pubmed: 33927376
J Hematol Oncol. 2020 Sep 4;13(1):120
pubmed: 32887634
Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):
pubmed: 33688035
N Engl J Med. 2019 Nov 14;381(20):1897-1908
pubmed: 31722150
J Immunol. 2010 Dec 15;185(12):7262-73
pubmed: 21076059
J Gen Virol. 1991 May;72 ( Pt 5):1031-8
pubmed: 2033387
Vaccine. 1994 Aug;12(11):1032-40
pubmed: 7975844
Vaccines (Basel). 2021 Feb 06;9(2):
pubmed: 33562141
Lancet Infect Dis. 2020 Jul;20(7):827-838
pubmed: 32325037
J Virol. 2014 May;88(10):5277-86
pubmed: 24574414
PLoS One. 2009;4(1):e4180
pubmed: 19159014
J Infect Dis. 2011 Mar 1;203(5):610-9
pubmed: 21282192
Cancer Res. 2013 Feb 15;73(4):1265-75
pubmed: 23393196
Vaccine. 2021 May 21;39(22):3067-3080
pubmed: 33077299
J Immunol. 2010 Jan 1;184(1):45-55
pubmed: 19949110
Comput Struct Biotechnol J. 2020;18:3402-3414
pubmed: 33200028
Nat Struct Mol Biol. 2020 Oct;27(10):925-933
pubmed: 32699321
Biosci Rep. 2021 Aug 27;41(8):
pubmed: 34328172
J Virol. 1992 May;66(5):2617-30
pubmed: 1560521
Mol Ther Oncolytics. 2017 Dec 05;8:27-40
pubmed: 29367944
Appl Microbiol Biotechnol. 2007 Oct;76(5):1131-6
pubmed: 17581748
Nature. 2020 Dec;588(7839):682-687
pubmed: 33045718
Angew Chem Int Ed Engl. 2021 Apr 26;60(18):10273-10278
pubmed: 33684258
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6641-6
pubmed: 15096611
Virology. 1998 May 10;244(2):365-96
pubmed: 9601507
Virology. 2015 Jan 15;475:1-14
pubmed: 25462341
Nat Commun. 2020 Nov 30;11(1):6121
pubmed: 33257686
Science. 2020 Jul 17;369(6501):330-333
pubmed: 32366695
Zoonoses Public Health. 2007;54(3-4):118-24
pubmed: 17456141
J Immunol. 2005 Apr 15;174(8):4908-15
pubmed: 15814718
Cell. 2020 Nov 12;183(4):1024-1042.e21
pubmed: 32991844
N Engl J Med. 2018 Feb 1;378(5):449-459
pubmed: 29385376
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Immunity. 2020 Dec 15;53(6):1245-1257.e5
pubmed: 33326767
PLoS One. 2017 Jan 3;12(1):e0169247
pubmed: 28046039
Nature. 2021 May;593(7857):136-141
pubmed: 33706364
Mol Ther Oncolytics. 2019 Jul 03;14:246-252
pubmed: 31428674
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
N Engl J Med. 2021 May 13;384(19):1824-1835
pubmed: 33440088
J Infect Dis. 2003 Apr 15;187(8):1319-22
pubmed: 12696013
Front Mol Biosci. 2021 Apr 22;8:671633
pubmed: 33968996