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Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection
Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.

computational design, glycans, immune-focusing, nanoparticle, RBD, SARS-CoV-2, SARS-CoV-2 Challenge, spike, structure-based design, vaccine
2211-1247
Konrath, Kylie M.
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Liaw, Kevin
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Wu, Yuanhan
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Zhu, Xizhou
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Walker, Susanne N.
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Xu, Ziyang
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Schultheis, Katherine
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Chokkalingam, Neethu
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Chawla, Himanshi
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Du, Jianqiu
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Tursi, Nicholas J.
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Moore, Alan
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Adolf-Bryfogle, Jared
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Purwar, Mansi
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Reuschel, Emma L.
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Frase, Drew
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Sullivan, Matthew
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Fry, Benjamin
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Maricic, Igor
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Andrade, Viviane M.
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Iffland, Christel
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Crispin, Max
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Broderick, Kate E.
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Humeau, Laurent M.P.F.
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Patel, Ami
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Pallesen, Jesper
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Weiner, David B.
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Kulp, Daniel W.
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Konrath, Kylie M.
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Liaw, Kevin
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Wu, Yuanhan
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Zhu, Xizhou
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Walker, Susanne N.
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Xu, Ziyang
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Schultheis, Katherine
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Chokkalingam, Neethu
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Chawla, Himanshi
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Du, Jianqiu
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Tursi, Nicholas J.
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Moore, Alan
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Adolf-Bryfogle, Jared
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Purwar, Mansi
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Reuschel, Emma L.
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Frase, Drew
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Sullivan, Matthew
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Fry, Benjamin
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Maricic, Igor
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Andrade, Viviane M.
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Iffland, Christel
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Crispin, Max
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Broderick, Kate E.
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Humeau, Laurent M.P.F.
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Patel, Ami
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Pallesen, Jesper
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Weiner, David B.
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Kulp, Daniel W.
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Konrath, Kylie M., Liaw, Kevin, Wu, Yuanhan, Zhu, Xizhou, Walker, Susanne N., Xu, Ziyang, Schultheis, Katherine, Chokkalingam, Neethu, Chawla, Himanshi, Du, Jianqiu, Tursi, Nicholas J., Moore, Alan, Adolf-Bryfogle, Jared, Purwar, Mansi, Reuschel, Emma L., Frase, Drew, Sullivan, Matthew, Fry, Benjamin, Maricic, Igor, Andrade, Viviane M., Iffland, Christel, Crispin, Max, Broderick, Kate E., Humeau, Laurent M.P.F., Patel, Ami, Pallesen, Jesper, Weiner, David B. and Kulp, Daniel W. (2022) Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection. Cell Reports, 38 (5), [110318]. (doi:10.1016/j.celrep.2022.110318).

Record type: Article

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.

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Accepted/In Press date: 7 January 2022
e-pub ahead of print date: 11 January 2022
Published date: 1 February 2022
Additional Information: Funding Information: The authors would like to thank the Wistar Institute Core facilities for providing care to the animals. We would like to acknowledge Dr. Jason S. McLellan for providing reagents for hamster serology. We would also like to thank Dr. Jared Adolf-Bryfogle for generously contributing GTM code to Rosetta for use in this project. This research, including design of nanoparticles, was supported by Wistar Coronavirus Discovery Fund, a CURE/PA Department of Health grant (SAP no. 4100083104 ), and a COVID/PA Department of Human Services grant (SAP no. 4100089371 ) awarded to D.W.K. The DNA immunizations were supported by NIH / NIAID CIVICs ( 75N93019C00051 ), Wistar Coronavirus Discovery Fund, Wistar SRA 16-4/Inovio Pharmaceuticals, and COVID/PA Department of Human Services (SAP no. 4100089371 ) awarded to D.B.W. This research was supported by Indiana University start-up funds to J.P. The funding sources were not involved in the design of this study, collection and analyses of data, or decision to submit the manuscript. Publisher Copyright: © 2022 The Authors Copyright: Copyright 2022 Elsevier B.V., All rights reserved.
Keywords: computational design, glycans, immune-focusing, nanoparticle, RBD, SARS-CoV-2, SARS-CoV-2 Challenge, spike, structure-based design, vaccine

Identifiers

Local EPrints ID: 455740
URI: http://eprints.soton.ac.uk/id/eprint/455740
DOI: doi:10.1016/j.celrep.2022.110318
ISSN: 2211-1247
PURE UUID: 35de254b-021f-419f-98be-78fb7dfb1414
ORCID for Himanshi Chawla: ORCID iD orcid.org/0000-0001-9828-6593
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 31 Mar 2022 16:50
Last modified: 18 Mar 2024 03:53

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Contributors

Author: Kylie M. Konrath
Author: Kevin Liaw
Author: Yuanhan Wu
Author: Xizhou Zhu
Author: Susanne N. Walker
Author: Ziyang Xu
Author: Katherine Schultheis
Author: Neethu Chokkalingam
Author: Himanshi Chawla ORCID iD
Author: Jianqiu Du
Author: Nicholas J. Tursi
Author: Alan Moore
Author: Jared Adolf-Bryfogle
Author: Mansi Purwar
Author: Emma L. Reuschel
Author: Drew Frase
Author: Matthew Sullivan
Author: Benjamin Fry
Author: Igor Maricic
Author: Viviane M. Andrade
Author: Christel Iffland
Author: Max Crispin ORCID iD
Author: Kate E. Broderick
Author: Laurent M.P.F. Humeau
Author: Ami Patel
Author: Jesper Pallesen
Author: David B. Weiner
Author: Daniel W. Kulp

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