Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine*.
Adjuvants, Immunologic
/ therapeutic use
Animals
COVID-19
/ prevention & control
COVID-19 Vaccines
/ immunology
Cholesterol
/ analogs & derivatives
Female
Humans
Imidazoles
/ immunology
Immunity, Innate
/ drug effects
Influenza A Virus, H1N1 Subtype
/ drug effects
Influenza Vaccines
/ immunology
Influenza, Human
/ prevention & control
Membrane Glycoproteins
/ agonists
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Polyethylene Glycols
/ therapeutic use
Quinolines
/ immunology
Recombinant Proteins
/ immunology
SARS-CoV-2
/ drug effects
Spike Glycoprotein, Coronavirus
/ immunology
Surface-Active Agents
/ therapeutic use
Toll-Like Receptor 7
/ agonists
Toll-Like Receptor 8
/ agonists
COVID-19
SARS-CoV-2
amphiphiles
innate immunity
vaccines
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
19 04 2021
19 04 2021
Historique:
revised:
24
12
2020
received:
17
11
2020
pubmed:
20
1
2021
medline:
21
4
2021
entrez:
19
1
2021
Statut:
ppublish
Résumé
The search for vaccines that protect from severe morbidity and mortality because of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is a race against the clock and the virus. Here we describe an amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol-poly(ethylene glycol) macromolecular amphiphile. It is water-soluble and exhibits massive translocation to lymph nodes upon local administration through binding to albumin, affording localized innate immune activation and reduction in systemic inflammation. The adjuvanticity of IMDQ-PEG-CHOL was validated in a licensed vaccine setting (quadrivalent influenza vaccine) and an experimental trimeric recombinant SARS-CoV-2 spike protein vaccine, showing robust IgG2a and IgG1 antibody titers in mice that could neutralize viral infection in vitro and in vivo in a mouse model.
Identifiants
pubmed: 33464672
doi: 10.1002/anie.202015362
pmc: PMC8014308
doi:
Substances chimiques
Adjuvants, Immunologic
0
COVID-19 Vaccines
0
Imidazoles
0
Influenza Vaccines
0
Membrane Glycoproteins
0
Quinolines
0
Recombinant Proteins
0
Spike Glycoprotein, Coronavirus
0
Surface-Active Agents
0
TLR8 protein, mouse
0
Tlr7 protein, mouse
0
Toll-Like Receptor 7
0
Toll-Like Receptor 8
0
spike protein, SARS-CoV-2
0
Polyethylene Glycols
3WJQ0SDW1A
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9467-9473Subventions
Organisme : NIAID NIH HHS
ID : R21 AI157606
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00045
Pays : United States
Organisme : European Research Council
ID : 817938
Pays : International
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI124297
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI097092
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00051
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : ErratumIn
Informations de copyright
© 2021 Wiley-VCH GmbH.
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