SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination.
Angiotensin-Converting Enzyme 2
/ immunology
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Binding Sites
COVID-19
/ immunology
Female
HEK293 Cells
Humans
Immunogenicity, Vaccine
/ immunology
Mice
Pandemics
/ prevention & control
Rabbits
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
Vaccination
Virus Replication
/ drug effects
COVID-19
SARS-CoV-2
antigens
liposomes
nanoparticles
vaccines
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
20
08
2020
revised:
25
09
2020
pubmed:
29
10
2020
medline:
9
1
2021
entrez:
28
10
2020
Statut:
ppublish
Résumé
The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a candidate vaccine antigen that binds angiotensin-converting enzyme 2 (ACE2), leading to virus entry. Here, it is shown that rapid conversion of recombinant RBD into particulate form via admixing with liposomes containing cobalt-porphyrin-phospholipid (CoPoP) potently enhances the functional antibody response. Antigen binding via His-tag insertion into the CoPoP bilayer results in a serum-stable and conformationally intact display of the RBD on the liposome surface. Compared to other vaccine formulations, immunization using CoPoP liposomes admixed with recombinant RBD induces multiple orders of magnitude higher levels of antibody titers in mice that neutralize pseudovirus cell entry, block RBD interaction with ACE2, and inhibit live virus replication. Enhanced immunogenicity can be accounted for by greater RBD uptake into antigen-presenting cells in particulate form and improved immune cell infiltration in draining lymph nodes. QS-21 inclusion in the liposomes results in an enhanced antigen-specific polyfunctional T cell response. In mice, high dose immunization results in minimal local reactogenicity, is well-tolerated, and does not elevate serum cobalt levels. Taken together, these results confirm that particulate presentation strategies for the RBD immunogen should be considered for inducing strongly neutralizing antibody responses against SARS-CoV-2.
Identifiants
pubmed: 33111375
doi: 10.1002/adma.202005637
pmc: PMC7645956
mid: NIHMS1642570
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Spike Glycoprotein, Coronavirus
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
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2005637Subventions
Organisme : NIAID NIH HHS
ID : R01 AI148557
Pays : United States
Organisme : Quebec Government
Organisme : McGill University
Organisme : NCI NIH HHS
ID : R01 CA247771
Pays : United States
Organisme : NIH HHS
ID : R01AI148557
Pays : United States
Organisme : NIH HHS
ID : R01CA247771
Pays : United States
Organisme : Canada Foundation for Innovation
Organisme : NIH HHS
ID : R01AI148557
Pays : United States
Organisme : NIH HHS
ID : R01CA247771
Pays : United States
Informations de copyright
© 2020 Wiley-VCH GmbH.
Références
J Exp Med. 2010 Apr 12;207(4):823-36
pubmed: 20351058
Cell. 2020 Nov 25;183(5):1367-1382.e17
pubmed: 33160446
Vaccine. 2020 Jan 22;38(4):942-950
pubmed: 31727504
J Virol. 2004 Jun;78(11):5535-45
pubmed: 15140950
Ann Emerg Med. 2001 Jun;37(6):635-41
pubmed: 11385334
Nat Chem. 2015 May;7(5):438-46
pubmed: 25901823
Nat Nanotechnol. 2018 Dec;13(12):1174-1181
pubmed: 30297818
Vaccine. 2011 Feb 17;29(9):1812-23
pubmed: 21215831
Int J Pharm. 2020 Nov 15;589:119843
pubmed: 32890653
Adv Mater. 2020 Dec;32(50):e2005637
pubmed: 33111375
Lancet Infect Dis. 2020 Sep;20(9):e238-e244
pubmed: 32628905
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2536-41
pubmed: 14983044
Sci Transl Med. 2017 Jun 7;9(393):
pubmed: 28592561
Nat Commun. 2020 May 4;11(1):2251
pubmed: 32366817
NPJ Vaccines. 2020 Mar 18;5(1):23
pubmed: 32218995
Nature. 2020 Oct;586(7830):572-577
pubmed: 32726802
Viruses. 2020 Jan 24;12(2):
pubmed: 31991541
Cell. 2020 Aug 6;182(3):722-733.e11
pubmed: 32645327
Science. 2020 May 8;368(6491):630-633
pubmed: 32245784
J Exp Med. 2009 Dec 21;206(13):3115-30
pubmed: 20008528
J Clin Invest. 2020 Dec 1;130(12):6728-6738
pubmed: 32910806
Eur J Immunol. 2008 Feb;38(2):350-63
pubmed: 18200635
Sci Rep. 2019 Jul 12;9(1):10090
pubmed: 31300682
Front Pharmacol. 2020 Jun 19;11:937
pubmed: 32636754
PLoS Med. 2006 Jul;3(7):e237
pubmed: 16796401
mBio. 2021 May 11;12(3):
pubmed: 33975938
Proc Natl Acad Sci U S A. 2020 May 26;117(21):11727-11734
pubmed: 32376634
Cell Mol Immunol. 2020 Jun;17(6):613-620
pubmed: 32203189
Vaccine. 2009 Mar 18;27(13):1881-8
pubmed: 19368767
Emerg Infect Dis. 2020 Jun;26(6):1266-1273
pubmed: 32160149
Vaccine. 2012 Aug 3;30(36):5373-81
pubmed: 22728225
Eur J Immunol. 2013 Jul;43(7):1706-15
pubmed: 23553052
Mayo Clin Proc. 2020 Oct;95(10):2172-2188
pubmed: 33012348