Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Philip J.M. Brouwer; Mitch Brinkkemper; Pauline Maisonnasse; Nathalie Dereuddre-Bosquet; Marloes Grobben; Mathieu Claireaux; Marlon de Gast; Romain Marlin; Virginie Chesnais; Ségolène Diry; Joel D. Allen; Yasunori Watanabe; Julia M. Giezen; Gius Kerster; Hannah L. Turner; Karlijn van der Straten; Cynthia A. van der Linden; Yoann Aldon; Thibaut Naninck; Ilja Bontjer; Judith A. Burger; Meliawati Poniman; Anna Z. Mykytyn; Nisreen M.A. Okba; Edith E. Schermer; Marielle J. van Breemen; Rashmi Ravichandran; Tom G. Caniels; Jelle van Schooten; Nidhal Kahlaoui; Vanessa Contreras; Julien Lemaître; Catherine Chapon; Raphaël Ho Tsong Fang; Julien Villaudy; Kwinten Sliepen; Yme U. van der Velden; Bart L. Haagmans; Godelieve J. de Bree; Eric Ginoux; Andrew B. Ward; Max Crispin; Neil P. King; Sylvie van der Werf; Marit J. van Gils; Roger Le Grand; Rogier W. Sanders

doi:10.1016/j.cell.2021.01.035

Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Philip J.M. Brouwer
, Mitch Brinkkemper
, Pauline Maisonnasse
, Nathalie Dereuddre-Bosquet
, Marloes Grobben
, Mathieu Claireaux
, Marlon de Gast
, Romain Marlin
, Virginie Chesnais
, Ségolène Diry
, Joel D. Allen
, Yasunori Watanabe
, Julia M. Giezen
, Gius Kerster
, Hannah L. Turner
, Karlijn van der Straten
, Cynthia A. van der Linden
, Yoann Aldon
, Thibaut Naninck
, Ilja Bontjer

Judith A. Burger, Meliawati Poniman, Anna Z. Mykytyn, Nisreen M.A. Okba, Edith E. Schermer, Marielle J. van Breemen, Rashmi Ravichandran, Tom G. Caniels, Jelle van Schooten, Nidhal Kahlaoui, Vanessa Contreras, Julien Lemaître, Catherine Chapon, Raphaël Ho Tsong Fang, Julien Villaudy, Kwinten Sliepen, Yme U. van der Velden, Bart L. Haagmans, Godelieve J. de Bree, Eric Ginoux, Andrew B. Ward, Max Crispin, Neil P. King, Sylvie van der Werf, Marit J. van Gils, Roger Le Grand^*, Rogier W. Sanders

^*Corresponding author for this work

Virology

University of Amsterdam
Université Paris-Saclay
Life and Soft
University of Southampton
University of Oxford
Scripps Research Institute
University of Washington
AIMM Therapeutics BV
Université Paris Cité
Institut Pasteur Paris

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

152 Citations (Scopus)

154 Downloads (Pure)

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic. Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.

Original language	English
Pages (from-to)	1188-1200.e19
Journal	Cell
Volume	184
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2021.01.035
Publication status	Published - 4 Mar 2021

Bibliographical note

Funding Information:
We thank B. Delache, S. Langlois, J. Demilly, N. Dhooge, P. Le Calvez, M. Potier, F. Relouzat, J.M. Robert, T. Prot, and C. Dodan for the non-human primate experiments; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the qRT-PCR and ELISpot assays and preparation of reagents; B. Fert for her help with the CT scans; M. Barendji, J. Dinh, and E. Guyon for the non-human primate sample processing; S. Keyser for the transports organization; N. Dimant and B. Targat for their help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for their help with the logistics and safety management; and I. Mangeot for her help with resource management. Ramos B cells were obtained from Drs. L. Wu and V.N. KewalRaman through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH. We thank A. McGuire for kindly sharing the pRRL.EuB29 lentiviral vector to transduce Ramos B cells. We thank P. Bieniasz for kindly sharing the pHIV-1NL43?ENV-NanoLuc and SARS-CoV-2-S?19 plasmids and the 293T/ACE2 cell line. We thank H. Nijhuis for sample transportation. We thank A. Chung for sharing knowledge on the Luminex assay protocol and B. Wines and M. Hogarth for sharing the Fc?R dimers. We thank Antoine Nougairede for sharing the plasmid used for the sgRNA assay standardization. Finally, we thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion and MPLA liposome adjuvants. Animal images in Figures 3 and 4 were created with BioRender.com. This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici grant (to R.W.S.); the Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923, OPP1132237, and INV-002022 (to R.W.S. and/or N.P.K.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and OPP1170236 (to A.B.W.); the Fondation Dormeur, Vaduz (R.W.S. and to M.J.v.G.) and Health-Holland PPS-allowance LSHM20040 (to M.J.v.G.); the University of Southampton Coronavirus Response Fund (M.C.); and the Netherlands Organisation for Health Research and Development ZONMW (B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity. R.W.S. and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract 200421) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d'Avenir, managed by the National Research Agency (ANR) under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT's facilities and imaging technologies. The non-human primate study received financial support from REACTing, the ANR (AM-CoV-Path), and the European Infrastructure TRANSVAC2 (730964). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, methodology, validation, formal analysis, investigation, data curation, writing ? original draft, visualization, and project administration, P.J.M.B. M.B. and P.M.; methodology, investigation, formal analysis, supervision, validation, writing ? review & editing, N.D.B.; conceptualization, methodology, investigation, and writing ? original draft, M.G. M.C. M.d.G. J.D.A. and Y.W.; methodology, investigation, formal analysis, supervision, writing ? review & editing, R.M. V. Chesnais, and S.D.; formal analysis and writing ? original draft, T.N.; investigation, formal analysis, and writing ? review & editing, J.L.; investigation and writing ? original draft, G.K. J.M.G. H.T. and A.Z.M.; investigation, N.K. K.v.d.S. C.A.v.d.L. Y.A. I.B. J.A.B. M.P. E.E.S. M.J.v.B. T.G.C. J.v.S. N.M.A.O. and R.R.; conceptualization and writing ? original draft, K.S.; methodology, J.V.; conceptualization, methodology, supervision, and project administration, Y.U.v.d.V. and M.J.v.G.; resources and project administration, G.J.d.B.; supervision, V. Contreras; resources, supervision, and writing ? review & editing, C.C. R.H.T.F. B.L.H. N.P.K. M.C. and A.B.W.; resources and supervision, S.v.d.W. and E.G.; conceptualization, validation, resources, writing ? review & editing, supervision, project administration, and funding acquisition, R.L.G. and R.W.S. N.P.K. is a co-founder, shareholder, and chair of the scientific advisory board of Icosavax. The remaining authors declare no competing interests. Amsterdam UMC has filed a patent application concerning the SARS-CoV-2 mAbs used here (Brouwer et al. 2020). N.P.K. has a nonprovisional US patent (no. 14/930,792) related to I53-50 (Bale et al. 2016).

Funding Information:
We thank B. Delache, S. Langlois, J. Demilly, N. Dhooge, P. Le Calvez, M. Potier, F. Relouzat, J.M. Robert, T. Prot, and C. Dodan for the non-human primate experiments; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the qRT-PCR and ELISpot assays and preparation of reagents; B. Fert for her help with the CT scans; M. Barendji, J. Dinh, and E. Guyon for the non-human primate sample processing; S. Keyser for the transports organization; N. Dimant and B. Targat for their help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for their help with the logistics and safety management; and I. Mangeot for her help with resource management. Ramos B cells were obtained from Drs. L. Wu and V.N. KewalRaman through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH. We thank A. McGuire for kindly sharing the pRRL.EuB29 lentiviral vector to transduce Ramos B cells. We thank P. Bieniasz for kindly sharing the pHIV-1 NL43 ΔENV-NanoLuc and SARS-CoV-2-S Δ19 plasmids and the 293T/ACE2 cell line. We thank H. Nijhuis for sample transportation. We thank A. Chung for sharing knowledge on the Luminex assay protocol and B. Wines and M. Hogarth for sharing the FcγR dimers. We thank Antoine Nougairede for sharing the plasmid used for the sgRNA assay standardization. Finally, we thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion and MPLA liposome adjuvants. Animal images in Figures 3 and 4 were created with BioRender.com . This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici grant (to R.W.S.); the Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923 , OPP1132237 , and INV-002022 (to R.W.S. and/or N.P.K.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and OPP1170236 (to A.B.W.); the Fondation Dormeur, Vaduz (R.W.S. and to M.J.v.G.) and Health-Holland PPS-allowance LSHM20040 (to M.J.v.G.); the University of Southampton Coronavirus Response Fund (M.C.); and the Netherlands Organisation for Health Research and Development ZONMW (B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity . R.W.S. and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract 200421 ) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d’Avenir, managed by the National Research Agency (ANR) under reference ANR-11-INBS-0008 . The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The non-human primate study received financial support from REACTing , the ANR ( AM-CoV-Path ), and the European Infrastructure TRANSVAC2 ( 730964 ). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting.

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Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infectionFinal published version, 6.3 MBLicence: CC BY

Cite this

Brouwer, P. J. M., Brinkkemper, M., Maisonnasse, P., Dereuddre-Bosquet, N., Grobben, M., Claireaux, M., de Gast, M., Marlin, R., Chesnais, V., Diry, S., Allen, J. D., Watanabe, Y., Giezen, J. M., Kerster, G., Turner, H. L., van der Straten, K., van der Linden, C. A., Aldon, Y., Naninck, T., ... Sanders, R. W. (2021). Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection. Cell, 184(5), 1188-1200.e19. https://doi.org/10.1016/j.cell.2021.01.035

@article{962293443f6a4e72ad13ceb5ed8dc026,

title = "Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection",

abstract = "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic. Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.",

author = "Brouwer, \{Philip J.M.\} and Mitch Brinkkemper and Pauline Maisonnasse and Nathalie Dereuddre-Bosquet and Marloes Grobben and Mathieu Claireaux and \{de Gast\}, Marlon and Romain Marlin and Virginie Chesnais and S{\'e}gol{\`e}ne Diry and Allen, \{Joel D.\} and Yasunori Watanabe and Giezen, \{Julia M.\} and Gius Kerster and Turner, \{Hannah L.\} and \{van der Straten\}, Karlijn and \{van der Linden\}, \{Cynthia A.\} and Yoann Aldon and Thibaut Naninck and Ilja Bontjer and Burger, \{Judith A.\} and Meliawati Poniman and Mykytyn, \{Anna Z.\} and Okba, \{Nisreen M.A.\} and Schermer, \{Edith E.\} and \{van Breemen\}, \{Marielle J.\} and Rashmi Ravichandran and Caniels, \{Tom G.\} and \{van Schooten\}, Jelle and Nidhal Kahlaoui and Vanessa Contreras and Julien Lema{\^i}tre and Catherine Chapon and Fang, \{Rapha{\"e}l Ho Tsong\} and Julien Villaudy and Kwinten Sliepen and \{van der Velden\}, \{Yme U.\} and Haagmans, \{Bart L.\} and \{de Bree\}, \{Godelieve J.\} and Eric Ginoux and Ward, \{Andrew B.\} and Max Crispin and King, \{Neil P.\} and \{van der Werf\}, Sylvie and \{van Gils\}, \{Marit J.\} and \{Le Grand\}, Roger and Sanders, \{Rogier W.\}",

note = "Funding Information: We thank B. Delache, S. Langlois, J. Demilly, N. Dhooge, P. Le Calvez, M. Potier, F. Relouzat, J.M. Robert, T. Prot, and C. Dodan for the non-human primate experiments; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the qRT-PCR and ELISpot assays and preparation of reagents; B. Fert for her help with the CT scans; M. Barendji, J. Dinh, and E. Guyon for the non-human primate sample processing; S. Keyser for the transports organization; N. Dimant and B. Targat for their help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for their help with the logistics and safety management; and I. Mangeot for her help with resource management. Ramos B cells were obtained from Drs. L. Wu and V.N. KewalRaman through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH. We thank A. McGuire for kindly sharing the pRRL.EuB29 lentiviral vector to transduce Ramos B cells. We thank P. Bieniasz for kindly sharing the pHIV-1NL43?ENV-NanoLuc and SARS-CoV-2-S?19 plasmids and the 293T/ACE2 cell line. We thank H. Nijhuis for sample transportation. We thank A. Chung for sharing knowledge on the Luminex assay protocol and B. Wines and M. Hogarth for sharing the Fc?R dimers. We thank Antoine Nougairede for sharing the plasmid used for the sgRNA assay standardization. Finally, we thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion and MPLA liposome adjuvants. Animal images in Figures 3 and 4 were created with BioRender.com. This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici grant (to R.W.S.); the Bill \& Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923, OPP1132237, and INV-002022 (to R.W.S. and/or N.P.K.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and OPP1170236 (to A.B.W.); the Fondation Dormeur, Vaduz (R.W.S. and to M.J.v.G.) and Health-Holland PPS-allowance LSHM20040 (to M.J.v.G.); the University of Southampton Coronavirus Response Fund (M.C.); and the Netherlands Organisation for Health Research and Development ZONMW (B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity. R.W.S. and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract 200421) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d'Avenir, managed by the National Research Agency (ANR) under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT's facilities and imaging technologies. The non-human primate study received financial support from REACTing, the ANR (AM-CoV-Path), and the European Infrastructure TRANSVAC2 (730964). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, methodology, validation, formal analysis, investigation, data curation, writing ? original draft, visualization, and project administration, P.J.M.B. M.B. and P.M.; methodology, investigation, formal analysis, supervision, validation, writing ? review \& editing, N.D.B.; conceptualization, methodology, investigation, and writing ? original draft, M.G. M.C. M.d.G. J.D.A. and Y.W.; methodology, investigation, formal analysis, supervision, writing ? review \& editing, R.M. V. Chesnais, and S.D.; formal analysis and writing ? original draft, T.N.; investigation, formal analysis, and writing ? review \& editing, J.L.; investigation and writing ? original draft, G.K. J.M.G. H.T. and A.Z.M.; investigation, N.K. K.v.d.S. C.A.v.d.L. Y.A. I.B. J.A.B. M.P. E.E.S. M.J.v.B. T.G.C. J.v.S. N.M.A.O. and R.R.; conceptualization and writing ? original draft, K.S.; methodology, J.V.; conceptualization, methodology, supervision, and project administration, Y.U.v.d.V. and M.J.v.G.; resources and project administration, G.J.d.B.; supervision, V. Contreras; resources, supervision, and writing ? review \& editing, C.C. R.H.T.F. B.L.H. N.P.K. M.C. and A.B.W.; resources and supervision, S.v.d.W. and E.G.; conceptualization, validation, resources, writing ? review \& editing, supervision, project administration, and funding acquisition, R.L.G. and R.W.S. N.P.K. is a co-founder, shareholder, and chair of the scientific advisory board of Icosavax. The remaining authors declare no competing interests. Amsterdam UMC has filed a patent application concerning the SARS-CoV-2 mAbs used here (Brouwer et al. 2020). N.P.K. has a nonprovisional US patent (no. 14/930,792) related to I53-50 (Bale et al. 2016). Funding Information: We thank B. Delache, S. Langlois, J. Demilly, N. Dhooge, P. Le Calvez, M. Potier, F. Relouzat, J.M. Robert, T. Prot, and C. Dodan for the non-human primate experiments; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the qRT-PCR and ELISpot assays and preparation of reagents; B. Fert for her help with the CT scans; M. Barendji, J. Dinh, and E. Guyon for the non-human primate sample processing; S. Keyser for the transports organization; N. Dimant and B. Targat for their help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for their help with the logistics and safety management; and I. Mangeot for her help with resource management. Ramos B cells were obtained from Drs. L. Wu and V.N. KewalRaman through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH. We thank A. McGuire for kindly sharing the pRRL.EuB29 lentiviral vector to transduce Ramos B cells. We thank P. Bieniasz for kindly sharing the pHIV-1 NL43 ΔENV-NanoLuc and SARS-CoV-2-S Δ19 plasmids and the 293T/ACE2 cell line. We thank H. Nijhuis for sample transportation. We thank A. Chung for sharing knowledge on the Luminex assay protocol and B. Wines and M. Hogarth for sharing the FcγR dimers. We thank Antoine Nougairede for sharing the plasmid used for the sgRNA assay standardization. Finally, we thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion and MPLA liposome adjuvants. Animal images in Figures 3 and 4 were created with BioRender.com . This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici grant (to R.W.S.); the Bill \& Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923 , OPP1132237 , and INV-002022 (to R.W.S. and/or N.P.K.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and OPP1170236 (to A.B.W.); the Fondation Dormeur, Vaduz (R.W.S. and to M.J.v.G.) and Health-Holland PPS-allowance LSHM20040 (to M.J.v.G.); the University of Southampton Coronavirus Response Fund (M.C.); and the Netherlands Organisation for Health Research and Development ZONMW (B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity . R.W.S. and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract 200421 ) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d{\textquoteright}Avenir, managed by the National Research Agency (ANR) under reference ANR-11-INBS-0008 . The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT{\textquoteright}s facilities and imaging technologies. The non-human primate study received financial support from REACTing , the ANR ( AM-CoV-Path ), and the European Infrastructure TRANSVAC2 ( 730964 ). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = mar,

day = "4",

doi = "10.1016/j.cell.2021.01.035",

language = "English",

volume = "184",

pages = "1188--1200.e19",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "5",

}

Brouwer, PJM, Brinkkemper, M, Maisonnasse, P, Dereuddre-Bosquet, N, Grobben, M, Claireaux, M, de Gast, M, Marlin, R, Chesnais, V, Diry, S, Allen, JD, Watanabe, Y, Giezen, JM, Kerster, G, Turner, HL, van der Straten, K, van der Linden, CA, Aldon, Y, Naninck, T, Bontjer, I, Burger, JA, Poniman, M, Mykytyn, AZ, Okba, NMA, Schermer, EE, van Breemen, MJ, Ravichandran, R, Caniels, TG, van Schooten, J, Kahlaoui, N, Contreras, V, Lemaître, J, Chapon, C, Fang, RHT, Villaudy, J, Sliepen, K, van der Velden, YU, Haagmans, BL, de Bree, GJ, Ginoux, E, Ward, AB, Crispin, M, King, NP, van der Werf, S, van Gils, MJ, Le Grand, R & Sanders, RW 2021, 'Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection', Cell, vol. 184, no. 5, pp. 1188-1200.e19. https://doi.org/10.1016/j.cell.2021.01.035

TY - JOUR

T1 - Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

AU - Brouwer, Philip J.M.

AU - Brinkkemper, Mitch

AU - Maisonnasse, Pauline

AU - Dereuddre-Bosquet, Nathalie

AU - Grobben, Marloes

AU - Claireaux, Mathieu

AU - de Gast, Marlon

AU - Marlin, Romain

AU - Chesnais, Virginie

AU - Diry, Ségolène

AU - Allen, Joel D.

AU - Watanabe, Yasunori

AU - Giezen, Julia M.

AU - Kerster, Gius

AU - Turner, Hannah L.

AU - van der Straten, Karlijn

AU - van der Linden, Cynthia A.

AU - Aldon, Yoann

AU - Naninck, Thibaut

AU - Bontjer, Ilja

AU - Burger, Judith A.

AU - Poniman, Meliawati

AU - Mykytyn, Anna Z.

AU - Okba, Nisreen M.A.

AU - Schermer, Edith E.

AU - van Breemen, Marielle J.

AU - Ravichandran, Rashmi

AU - Caniels, Tom G.

AU - van Schooten, Jelle

AU - Kahlaoui, Nidhal

AU - Contreras, Vanessa

AU - Lemaître, Julien

AU - Chapon, Catherine

AU - Fang, Raphaël Ho Tsong

AU - Villaudy, Julien

AU - Sliepen, Kwinten

AU - van der Velden, Yme U.

AU - Haagmans, Bart L.

AU - de Bree, Godelieve J.

AU - Ginoux, Eric

AU - Ward, Andrew B.

AU - Crispin, Max

AU - King, Neil P.

AU - van der Werf, Sylvie

AU - van Gils, Marit J.

AU - Le Grand, Roger

AU - Sanders, Rogier W.

N1 - Funding Information: We thank B. Delache, S. Langlois, J. Demilly, N. Dhooge, P. Le Calvez, M. Potier, F. Relouzat, J.M. Robert, T. Prot, and C. Dodan for the non-human primate experiments; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the qRT-PCR and ELISpot assays and preparation of reagents; B. Fert for her help with the CT scans; M. Barendji, J. Dinh, and E. Guyon for the non-human primate sample processing; S. Keyser for the transports organization; N. Dimant and B. Targat for their help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for their help with the logistics and safety management; and I. Mangeot for her help with resource management. Ramos B cells were obtained from Drs. L. Wu and V.N. KewalRaman through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH. We thank A. McGuire for kindly sharing the pRRL.EuB29 lentiviral vector to transduce Ramos B cells. We thank P. Bieniasz for kindly sharing the pHIV-1NL43?ENV-NanoLuc and SARS-CoV-2-S?19 plasmids and the 293T/ACE2 cell line. We thank H. Nijhuis for sample transportation. We thank A. Chung for sharing knowledge on the Luminex assay protocol and B. Wines and M. Hogarth for sharing the Fc?R dimers. We thank Antoine Nougairede for sharing the plasmid used for the sgRNA assay standardization. Finally, we thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion and MPLA liposome adjuvants. Animal images in Figures 3 and 4 were created with BioRender.com. This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici grant (to R.W.S.); the Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923, OPP1132237, and INV-002022 (to R.W.S. and/or N.P.K.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and OPP1170236 (to A.B.W.); the Fondation Dormeur, Vaduz (R.W.S. and to M.J.v.G.) and Health-Holland PPS-allowance LSHM20040 (to M.J.v.G.); the University of Southampton Coronavirus Response Fund (M.C.); and the Netherlands Organisation for Health Research and Development ZONMW (B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity. R.W.S. and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract 200421) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d'Avenir, managed by the National Research Agency (ANR) under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT's facilities and imaging technologies. The non-human primate study received financial support from REACTing, the ANR (AM-CoV-Path), and the European Infrastructure TRANSVAC2 (730964). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, methodology, validation, formal analysis, investigation, data curation, writing ? original draft, visualization, and project administration, P.J.M.B. M.B. and P.M.; methodology, investigation, formal analysis, supervision, validation, writing ? review & editing, N.D.B.; conceptualization, methodology, investigation, and writing ? original draft, M.G. M.C. M.d.G. J.D.A. and Y.W.; methodology, investigation, formal analysis, supervision, writing ? review & editing, R.M. V. Chesnais, and S.D.; formal analysis and writing ? original draft, T.N.; investigation, formal analysis, and writing ? review & editing, J.L.; investigation and writing ? original draft, G.K. J.M.G. H.T. and A.Z.M.; investigation, N.K. K.v.d.S. C.A.v.d.L. Y.A. I.B. J.A.B. M.P. E.E.S. M.J.v.B. T.G.C. J.v.S. N.M.A.O. and R.R.; conceptualization and writing ? original draft, K.S.; methodology, J.V.; conceptualization, methodology, supervision, and project administration, Y.U.v.d.V. and M.J.v.G.; resources and project administration, G.J.d.B.; supervision, V. Contreras; resources, supervision, and writing ? review & editing, C.C. R.H.T.F. B.L.H. N.P.K. M.C. and A.B.W.; resources and supervision, S.v.d.W. and E.G.; conceptualization, validation, resources, writing ? review & editing, supervision, project administration, and funding acquisition, R.L.G. and R.W.S. N.P.K. is a co-founder, shareholder, and chair of the scientific advisory board of Icosavax. The remaining authors declare no competing interests. Amsterdam UMC has filed a patent application concerning the SARS-CoV-2 mAbs used here (Brouwer et al. 2020). N.P.K. has a nonprovisional US patent (no. 14/930,792) related to I53-50 (Bale et al. 2016). Funding Information: We thank B. Delache, S. Langlois, J. Demilly, N. Dhooge, P. Le Calvez, M. Potier, F. Relouzat, J.M. Robert, T. Prot, and C. Dodan for the non-human primate experiments; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the qRT-PCR and ELISpot assays and preparation of reagents; B. Fert for her help with the CT scans; M. Barendji, J. Dinh, and E. Guyon for the non-human primate sample processing; S. Keyser for the transports organization; N. Dimant and B. Targat for their help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for their help with the logistics and safety management; and I. Mangeot for her help with resource management. Ramos B cells were obtained from Drs. L. Wu and V.N. KewalRaman through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH. We thank A. McGuire for kindly sharing the pRRL.EuB29 lentiviral vector to transduce Ramos B cells. We thank P. Bieniasz for kindly sharing the pHIV-1 NL43 ΔENV-NanoLuc and SARS-CoV-2-S Δ19 plasmids and the 293T/ACE2 cell line. We thank H. Nijhuis for sample transportation. We thank A. Chung for sharing knowledge on the Luminex assay protocol and B. Wines and M. Hogarth for sharing the FcγR dimers. We thank Antoine Nougairede for sharing the plasmid used for the sgRNA assay standardization. Finally, we thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion and MPLA liposome adjuvants. Animal images in Figures 3 and 4 were created with BioRender.com . This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici grant (to R.W.S.); the Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923 , OPP1132237 , and INV-002022 (to R.W.S. and/or N.P.K.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and OPP1170236 (to A.B.W.); the Fondation Dormeur, Vaduz (R.W.S. and to M.J.v.G.) and Health-Holland PPS-allowance LSHM20040 (to M.J.v.G.); the University of Southampton Coronavirus Response Fund (M.C.); and the Netherlands Organisation for Health Research and Development ZONMW (B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity . R.W.S. and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract 200421 ) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d’Avenir, managed by the National Research Agency (ANR) under reference ANR-11-INBS-0008 . The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The non-human primate study received financial support from REACTing , the ANR ( AM-CoV-Path ), and the European Infrastructure TRANSVAC2 ( 730964 ). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Publisher Copyright: © 2021 The Authors

PY - 2021/3/4

Y1 - 2021/3/4

N2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic. Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.

AB - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic. Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.

UR - https://www.scopus.com/pages/publications/85100744149

U2 - 10.1016/j.cell.2021.01.035

DO - 10.1016/j.cell.2021.01.035

M3 - Article

C2 - 33577765

AN - SCOPUS:85100744149

SN - 0092-8674

VL - 184

SP - 1188-1200.e19

JO - Cell

JF - Cell

IS - 5

ER -

Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

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