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.
Bibliographical noteFunding Information:
This work was partly funded by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract no. HHSN272201400008C), by SEM-CIVIC, a NIAID funded Collaborative Influenza Vaccine Innovation Center (contract no. 75N93019C00051), by a supplement to NIAID contract 75N93019C00045, by NIAID grants U01AI124297 and P01AI097092, by FASTGRANT 2176, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020?215611 (5384)) and anonymous donors to A.G.-S. This work was supported in part by NIAID R21AI157606 (L.C.). Work in the Krammer laboratory was supported by the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C (F.K., for reagent generation), Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 (F.K., for reagent generation), and the generous support of the JPB foundation, the Open Philanthropy Project (no. 2020?215611) and other philanthropic donations. B.G.D.G. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant N 817938). We also thank Randy Albrecht and Carles Martinez for support with the BSL3 facility and procedures at the ISMMS and Richard Cadagan for excellent technical assistance.
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