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Here we describe an amphiphilic imidazoquinoline (IMDQ\u2010PEG\u2010CHOL) TLR7\/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol\u2010poly(ethylene glycol) macromolecular amphiphile. It is water\u2010soluble 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\u2010PEG\u2010CHOL was validated in a licensed vaccine setting (quadrivalent influenza vaccine) and an experimental trimeric recombinant SARS\u2010CoV\u20102 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.<\/jats:p>","DOI":"10.1002\/anie.202015362","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T13:26:59Z","timestamp":1611062819000},"page":"9467-9473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Sterilizing Immunity against SARS\u2010CoV\u20102 Infection in Mice by a Single\u2010Shot and Lipid Amphiphile Imidazoquinoline TLR7\/8 Agonist\u2010Adjuvanted Recombinant Spike Protein Vaccine**"],"prefix":"10.1002","volume":"60","author":[{"given":"Sonia","family":"Jangra","sequence":"first","affiliation":[{"name":"Department of Microbiology Icahn 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