A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection.
Aged
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Antibodies, Neutralizing
/ blood
Antibodies, Viral
/ blood
COVID-19
/ mortality
COVID-19 Vaccines
/ genetics
Cell Line, Tumor
Chick Embryo
Chlorocebus aethiops
Cytokines
/ analysis
Female
HeLa Cells
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Plasmids
/ genetics
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ genetics
Vaccine Efficacy
Vaccines, DNA
/ genetics
Vaccinia virus
/ immunology
Vero Cells
Viral Vaccines
/ genetics
MVA vector
SARS-CoV-2 vaccine
mouse model
prefusion-stabilized S protein
protective efficacy
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
11
2021
accepted:
30
12
2021
entrez:
14
2
2022
pubmed:
15
2
2022
medline:
24
2
2022
Statut:
epublish
Résumé
We generated an optimized COVID-19 vaccine candidate based on the modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, termed MVA-CoV2-S(3P). The S(3P) protein was expressed at higher levels (2-fold) than the non-stabilized S in cells infected with the corresponding recombinant MVA viruses. One single dose of MVA-CoV2-S(3P) induced higher IgG and neutralizing antibody titers against parental SARS-CoV-2 and variants of concern than MVA-CoV2-S in wild-type C57BL/6 and in transgenic K18-hACE2 mice. In immunized C57BL/6 mice, two doses of MVA-CoV2-S or MVA-CoV2-S(3P) induced similar levels of SARS-CoV-2-specific B- and T-cell immune responses. Remarkably, a single administration of MVA-CoV2-S(3P) protected all K18-hACE2 mice from morbidity and mortality caused by SARS-CoV-2 infection, reducing SARS-CoV-2 viral loads, histopathological lesions, and levels of pro-inflammatory cytokines in the lungs. These results demonstrated that expression of a novel full-length prefusion-stabilized SARS-CoV-2 S protein by the MVA poxvirus vector enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, further supporting MVA-CoV2-S(3P) as an optimized vaccine candidate for clinical trials.
Identifiants
pubmed: 35154086
doi: 10.3389/fimmu.2021.824728
pmc: PMC8829548
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Cytokines
0
MVA vaccine
0
Spike Glycoprotein, Coronavirus
0
Vaccines, DNA
0
Viral Vaccines
0
spike protein, SARS-CoV-2
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
824728Informations de copyright
Copyright © 2022 Pérez, Lázaro-Frías, Zamora, Sánchez-Cordón, Astorgano, Luczkowiak, Delgado, Casasnovas, Esteban and García-Arriaza.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Euro Surveill. 2021 Jun;26(24):
pubmed: 34142653
Vaccines (Basel). 2020 Feb 06;8(1):
pubmed: 32041218
Nat Commun. 2021 Jan 11;12(1):244
pubmed: 33431842
Cell Host Microbe. 2020 Jul 8;28(1):124-133.e4
pubmed: 32485164
J Virol. 2021 Jan 7;:
pubmed: 33414159
Immunotherapy. 2020 Dec;12(17):1247-1255
pubmed: 32900263
Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):
pubmed: 33688035
Nat Commun. 2020 Nov 30;11(1):6121
pubmed: 33257686
Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7348-E7357
pubmed: 28807998
Cell. 2021 Feb 18;184(4):861-880
pubmed: 33497610
Lancet. 2021 Jan 9;397(10269):99-111
pubmed: 33306989
Nature. 2021 Feb;590(7845):320-325
pubmed: 33260195
Proc Natl Acad Sci U S A. 2021 Jul 13;118(28):
pubmed: 34162739
Euro Surveill. 2020 Jan;25(3):
pubmed: 31992387
J Clin Microbiol. 2020 Oct 21;58(11):
pubmed: 32826322
Nature. 2020 Oct;586(7830):594-599
pubmed: 32998157
Cell. 2020 Jun 25;181(7):1489-1501.e15
pubmed: 32473127
Am J Trop Med Hyg. 2020 Sep;103(3):1215-1219
pubmed: 32723427
J Virol. 2000 Jun;74(11):5091-100
pubmed: 10799583
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Vaccine. 2008 Jan 24;26(4):486-93
pubmed: 18155813
Cell. 2020 Nov 12;183(4):996-1012.e19
pubmed: 33010815
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Science. 2020 Jul 3;369(6499):77-81
pubmed: 32376603
Nat Rev Immunol. 2020 Sep;20(9):529-536
pubmed: 32728222
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
J Med Virol. 2021 Jan;93(1):144-148
pubmed: 32603501
Nat Rev Immunol. 2020 May;20(5):277
pubmed: 32249847
NPJ Vaccines. 2021 Apr 16;6(1):57
pubmed: 33863911
J Virol. 2018 May 14;92(11):
pubmed: 29514907
Immunity. 2021 Mar 9;54(3):542-556.e9
pubmed: 33631118
N Engl J Med. 2021 Feb 4;384(5):403-416
pubmed: 33378609
Vaccines (Basel). 2019 Dec 06;7(4):
pubmed: 31817622
Indian J Med Res. 2021 Jan & Feb;153(1 & 2):93-114
pubmed: 33361645
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
J Med Virol. 2020 Oct;92(10):2096-2104
pubmed: 32383254
Sci Rep. 2018 Nov 26;8(1):17385
pubmed: 30478418
Adv Virus Res. 2017;97:187-243
pubmed: 28057259
mBio. 2021 Oct 26;12(5):e0190821
pubmed: 34544278
mBio. 2021 Mar 2;12(2):
pubmed: 33653892
PLoS One. 2021 Sep 9;16(9):e0257191
pubmed: 34499677
Curr Opin Immunol. 2021 Aug;71:27-33
pubmed: 33873076
Zentralbl Bakteriol B. 1978 Dec;167(5-6):375-90
pubmed: 219640
Expert Rev Vaccines. 2013 Dec;12(12):1395-416
pubmed: 24168097
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
Am J Pathol. 2020 Nov;190(11):2290-2303
pubmed: 32795424
Immunity. 2020 Jun 16;52(6):971-977.e3
pubmed: 32413330
J Virol. 2013 Jul;87(13):7282-300
pubmed: 23596307
PLoS Pathog. 2021 May 20;17(5):e1009576
pubmed: 34015061
J Gen Virol. 2013 Dec;94(Pt 12):2771-2776
pubmed: 24077296
Vaccines (Basel). 2021 Apr 01;9(4):
pubmed: 33915773
PLoS One. 2010 Aug 24;5(8):e12395
pubmed: 20811493
N Engl J Med. 2020 Dec 31;383(27):2603-2615
pubmed: 33301246
Nat Commun. 2021 Jan 14;12(1):372
pubmed: 33446655
Sci Rep. 2018 Oct 24;8(1):15701
pubmed: 30356097
J Virol. 2000 Jan;74(2):923-33
pubmed: 10623755
Front Immunol. 2021 Jun 23;12:708820
pubmed: 34249017
J Virol. 2014 Mar;88(6):3527-47
pubmed: 24403588
Nature. 2020 Mar;579(7798):265-269
pubmed: 32015508
Nat Immunol. 2020 Nov;21(11):1327-1335
pubmed: 32839612