Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 17, Pages 9467-9473Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202015362
Keywords
amphiphiles; COVID-19; innate immunity; SARS-CoV-2; vaccines
Categories
Funding
- CRIP (Center for Research on Influenza Pathogenesis), a NIAID [HHSN272201400008C]
- SEM-CIVIC, a NIAID [75N93019C00051]
- FASTGRANT [2176]
- JPB Foundation
- Open Philanthropy Project [2020-215611 (5384)]
- NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) [HHSN272201400008C]
- Collaborative Influenza Vaccine Innovation Centers (CIVIC) [75N93019C00051]
- European Research Council (ERC) under the European Union [817938]
- European Research Council (ERC) [817938] Funding Source: European Research Council (ERC)
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IMDQ-PEG-CHOL is an amphiphilic TLR7/8 adjuvant that can enhance immune response, reduce systemic inflammation, and translocate to lymph nodes. When added to vaccines, it induces high levels of antibodies in mice that effectively neutralize viral infections in vitro and in vivo.
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.
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