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 |
|---|---|
| Article number | 365726 |
| Pages (from-to) | 1188-1200.e19 |
| Number of pages | 36 |
| Journal | Cell |
| Volume | 184 |
| Issue number | 5 |
| Early online date | 2021 |
| DOIs | |
| Publication status | Published - 4 Mar 2021 |
Keywords
- B cells
- COVID-19
- SARS-CoV-2
- antibodies
- immunity
- macaques
- nanoparticles
- protection
- vaccine
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In: Cell, Vol. 184, No. 5, 365726, 04.03.2021, p. 1188-1200.e19.
Research output: Contribution to journal › Article › Academic
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, S. golène
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 - Brouwer PJM, Brinkkemper M, Maisonnasse P, Dereuddre-Bosquet N, Grobben M, Claireaux M et al. Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection. bioRxiv. 2020 Nov 8. 365726. https://doi.org/10.1101/2020.11.07.365726 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 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
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.
KW - B cells
KW - COVID-19
KW - SARS-CoV-2
KW - antibodies
KW - immunity
KW - macaques
KW - nanoparticles
KW - protection
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85100744149&partnerID=8YFLogxK
U2 - https://doi.org/10.1101/2020.11.07.365726
DO - https://doi.org/10.1101/2020.11.07.365726
M3 - Article
C2 - 33577765
SN - 0092-8674
VL - 184
SP - 1188-1200.e19
JO - Cell
JF - Cell
IS - 5
M1 - 365726
ER -