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; Jana De Vrieze; Angela Choi; Raveen Rathnasinghe; Gabriel Laghlali; Annemiek Uvyn; Simon Van Herck; Lutz Nuhn; Kim Deswarte; Zifu Zhong; Niek N. Sanders; Stefan Lienenklaus; Sunil A. David; Shirin Strohmeier; Fatima Amanat; Florian Krammer; Hamida Hammad; Bart N. Lambrecht; Lynda Coughlan; Adolfo García-Sastre; Bruno G. De Geest; Michael Schotsaert

doi:10.1002/anie.202015362

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, Jana De Vrieze, Angela Choi, Raveen Rathnasinghe, Gabriel Laghlali, Annemiek Uvyn, Simon Van Herck, Lutz Nuhn, Kim Deswarte, Zifu Zhong, Niek N. Sanders, Stefan Lienenklaus, Sunil A. David, Shirin Strohmeier, Fatima Amanat, Florian Krammer, Hamida Hammad, Bart N. Lambrecht, Lynda Coughlan, Adolfo García-SastreBruno G. De Geest, Michael Schotsaert^*

^*Corresponding author for this work

Pulmonary Medicine

Research output: Contribution to journal › Article › Academic › peer-review

49 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	9467-9473
Number of pages	7
Journal	Angewandte Chemie - International Edition
Volume	60
Issue number	17
Early online date	19 Jan 2021
DOIs	https://doi.org/10.1002/anie.202015362
Publication status	Published - 9 Apr 2021

Bibliographical note

Funding 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.

Publisher Copyright: © 2021 Wiley-VCH GmbH

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Jangra, S., De Vrieze, J., Choi, A., Rathnasinghe, R., Laghlali, G., Uvyn, A., Van Herck, S., Nuhn, L., Deswarte, K., Zhong, Z., Sanders, N. N., Lienenklaus, S., David, S. A., Strohmeier, S., Amanat, F., Krammer, F., Hammad, H., Lambrecht, B. N., Coughlan, L., ... Schotsaert, M. (2021). 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**. Angewandte Chemie - International Edition, 60(17), 9467-9473. https://doi.org/10.1002/anie.202015362

@article{831d8e070bfc4892bd4ed16304da59ef,

title = "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**",

abstract = "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.",

author = "Sonia Jangra and {De Vrieze}, Jana and Angela Choi and Raveen Rathnasinghe and Gabriel Laghlali and Annemiek Uvyn and {Van Herck}, Simon and Lutz Nuhn and Kim Deswarte and Zifu Zhong and Sanders, {Niek N.} and Stefan Lienenklaus and David, {Sunil A.} and Shirin Strohmeier and Fatima Amanat and Florian Krammer and Hamida Hammad and Lambrecht, {Bart N.} and Lynda Coughlan and Adolfo Garc{\'i}a-Sastre and {De Geest}, {Bruno G.} and Michael Schotsaert",

note = "Funding 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. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",

year = "2021",

month = apr,

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doi = "10.1002/anie.202015362",

language = "English",

volume = "60",

pages = "9467--9473",

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Jangra, S, De Vrieze, J, Choi, A, Rathnasinghe, R, Laghlali, G, Uvyn, A, Van Herck, S, Nuhn, L, Deswarte, K, Zhong, Z, Sanders, NN, Lienenklaus, S, David, SA, Strohmeier, S, Amanat, F, Krammer, F, Hammad, H, Lambrecht, BN, Coughlan, L, García-Sastre, A, De Geest, BG & Schotsaert, M 2021, '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**', Angewandte Chemie - International Edition, vol. 60, no. 17, pp. 9467-9473. https://doi.org/10.1002/anie.202015362

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**. / Jangra, Sonia; De Vrieze, Jana; Choi, Angela et al.
In: Angewandte Chemie - International Edition, Vol. 60, No. 17, 09.04.2021, p. 9467-9473.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - 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**

AU - Jangra, Sonia

AU - De Vrieze, Jana

AU - Choi, Angela

AU - Rathnasinghe, Raveen

AU - Laghlali, Gabriel

AU - Uvyn, Annemiek

AU - Van Herck, Simon

AU - Nuhn, Lutz

AU - Deswarte, Kim

AU - Zhong, Zifu

AU - Sanders, Niek N.

AU - Lienenklaus, Stefan

AU - David, Sunil A.

AU - Strohmeier, Shirin

AU - Amanat, Fatima

AU - Krammer, Florian

AU - Hammad, Hamida

AU - Lambrecht, Bart N.

AU - Coughlan, Lynda

AU - García-Sastre, Adolfo

AU - De Geest, Bruno G.

AU - Schotsaert, Michael

N1 - Funding 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. Publisher Copyright: © 2021 Wiley-VCH GmbH

PY - 2021/4/9

Y1 - 2021/4/9

N2 - 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.

AB - 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.

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DO - 10.1002/anie.202015362

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JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

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ER -

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**

Abstract

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