Angew Chem Int Ed Engl . 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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Angew Chem Int Ed Engl


. 2021 Jan 19.
doi: 10.1002/anie.202015362. Online ahead of print.
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


Sonia Jangra ¹ , Jana De Vrieze ² , Angela Choi ¹ , Raveen Rathnasinghe ¹ , Gabriel Laghlali ¹ , Annemiek Uvyn ³ , Simon Van Herck ⁴ , Lutz Nuhn ⁵ , Kim Deswarte ⁶ , Zifu Zhong ² , Niek Sanders ⁷ , Stefan Lienenklaus ⁸ , Sunil David ⁹ , Shirin Strohmeier ¹ , Fatima Amanat ¹ , Florian Krammer ¹ , Hamida Hammad ⁶ , Bart N Lambrecht ⁶ , Lynda Coughlan ¹ , Adolfo Garc?a-Sastre ¹ , Bruno de Geest ¹⁰ , Michael Schotsaert ¹



Affiliations

• PMID: 33464672
• DOI: 10.1002/anie.202015362

Abstract

The search for vaccines that protect from severe morbidity and mortality as a result 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 the use of a novel 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. This amphiphile is water soluble and exhibits massive translocation to lymph nodes upon local administration, likely through binding to albumin, affording localized innate immune activation and a dramatic reduction in systemic inflammation. The adjuvanticity of IMDQ-PEG-CHOL was validated in the context of a licensed vaccine setting (i.e. the 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.

Keywords: vaccines, amphiphiles, innate immunity, SARS-CoV-2, COVID-19.