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