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**
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**
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DOI：
10.1002/anie.202015362
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发表时间：
2021-03-11
影响因子：
16.6
通讯作者：
Schotsaert, Michael
中科院分区：
文献类型：
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作者：
Jangra, Sonia;De Vrieze, Jana;Schotsaert, Michael
寻找预防因感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)而导致严重发病率和死亡率的疫苗(新冠肺炎)是一场与时间和病毒的赛跑。在这里，我们描述了一种两亲性咪唑喹啉(IMDQ-PEG-Chol)TLR7/8佐剂，它由连接到胆固醇-聚乙二醇大分子两亲性链端的咪唑喹啉组成。它是水溶性的，在局部给药时通过与白蛋白结合而大量转移到淋巴结，提供局部的先天免疫激活和减少全身炎症。在许可的疫苗环境(四价流感疫苗)和实验性的三聚体重组SARS-CoV-2刺突蛋白疫苗中验证了IMDQ-PEG-Chol的佐剂活性，在小鼠中显示了强大的IgG2a和IgG1抗体效价，可以在体外和体内中和病毒感染。
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.