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Sterilizing immunity against SARSU+2010CoVU+20102 infection in mice by a singleU+2010shot and lipid amphiphile imidazoquinoline TLR7/8 agonistU+2010adjuvanted recombinant spike protein vaccine**

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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.
Tijdschrift: Angewandte Chemie International Edition
ISSN: 1433-7851
Issue: 17
Volume: 60
Pagina's: 9467 - 9473
Jaar van publicatie:2021