The University of Southampton
×
Filter your search:
University of Southampton Institutional Repository

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.
ecb7ccee-bf0e-485e-a558-aa4f6c4b4e1b
Liaw, Kevin
51ab0b1c-3a52-400f-847c-1be42c579678
Wu, Yuanhan
88015362-29fe-47be-89c2-0684e4b673d5
Zhu, Xizhou
21c24a14-5c68-4a06-b760-e5328ad01971
Walker, Susanne N.
eec479eb-896b-40de-afbb-41bd1a4ceda7
Xu, Ziyang
906e7cdc-ead4-43c9-b54c-9769917e929b
Schultheis, Katherine
393bf91f-c1f4-4640-b06d-a4c53ee33cd0
Chokkalingam, Neethu
06e8e0b6-c47d-4352-87aa-ed5146584ac0
Chawla, Himanshi
07b9e983-4c35-4314-999d-fe3222a6c03b
Du, Jianqiu
21a8c35b-ed73-429f-bbe6-6607702fd67b
Tursi, Nicholas J.
65f64336-ac37-4edb-a7e9-9b7f9fc9f606
Moore, Alan
4101f1e4-b227-4ce3-890f-3b8162307129
Adolf-Bryfogle, Jared
2a006840-4b42-4ddf-9e71-78f02dfbaa0d
Purwar, Mansi
063aca9b-c778-479b-9596-aec0097b9e5b
Reuschel, Emma L.
8b7ea521-47d8-4f0a-ad10-a8876a0a551d
Frase, Drew
7e96f4cd-3020-4b38-bbaa-590501079927
Sullivan, Matthew
de408b1e-9187-467b-8c3d-4e2ba9d774d7
Fry, Benjamin
dc070eb1-8f2b-49a0-842a-15bc1fa6a1a4
Maricic, Igor
647da868-6ab9-4183-84a6-a7a1cf0e5bd9
Andrade, Viviane M.
042c2a5e-8875-4828-a4db-73c916a0c11e
Iffland, Christel
4760d9dd-59db-4394-ba3c-adb40cbcefb7
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Broderick, Kate E.
3ba0a1f9-4289-4b80-9e0c-fefe45d96634
Humeau, Laurent M.P.F.
d11afce4-70b7-400a-8350-2706aa6b50a0
Patel, Ami
37fcd585-68cd-44f3-b770-be3176eb0fd7
Pallesen, Jesper
4c823bd4-51f5-4b71-a1d4-ae9c1668ad78
Weiner, David B.
177ccd35-7ae1-40a3-b0f4-c984be75612b
Kulp, Daniel W.
3f4e260a-84f2-4140-b557-9bc3cb0947e7
Konrath, Kylie M.
ecb7ccee-bf0e-485e-a558-aa4f6c4b4e1b
Liaw, Kevin
51ab0b1c-3a52-400f-847c-1be42c579678
Wu, Yuanhan
88015362-29fe-47be-89c2-0684e4b673d5
Zhu, Xizhou
21c24a14-5c68-4a06-b760-e5328ad01971
Walker, Susanne N.
eec479eb-896b-40de-afbb-41bd1a4ceda7
Xu, Ziyang
906e7cdc-ead4-43c9-b54c-9769917e929b
Schultheis, Katherine
393bf91f-c1f4-4640-b06d-a4c53ee33cd0
Chokkalingam, Neethu
06e8e0b6-c47d-4352-87aa-ed5146584ac0
Chawla, Himanshi
07b9e983-4c35-4314-999d-fe3222a6c03b
Du, Jianqiu
21a8c35b-ed73-429f-bbe6-6607702fd67b
Tursi, Nicholas J.
65f64336-ac37-4edb-a7e9-9b7f9fc9f606
Moore, Alan
4101f1e4-b227-4ce3-890f-3b8162307129
Adolf-Bryfogle, Jared
2a006840-4b42-4ddf-9e71-78f02dfbaa0d
Purwar, Mansi
063aca9b-c778-479b-9596-aec0097b9e5b
Reuschel, Emma L.
8b7ea521-47d8-4f0a-ad10-a8876a0a551d
Frase, Drew
7e96f4cd-3020-4b38-bbaa-590501079927
Sullivan, Matthew
de408b1e-9187-467b-8c3d-4e2ba9d774d7
Fry, Benjamin
dc070eb1-8f2b-49a0-842a-15bc1fa6a1a4
Maricic, Igor
647da868-6ab9-4183-84a6-a7a1cf0e5bd9
Andrade, Viviane M.
042c2a5e-8875-4828-a4db-73c916a0c11e
Iffland, Christel
4760d9dd-59db-4394-ba3c-adb40cbcefb7
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Broderick, Kate E.
3ba0a1f9-4289-4b80-9e0c-fefe45d96634
Humeau, Laurent M.P.F.
d11afce4-70b7-400a-8350-2706aa6b50a0
Patel, Ami
37fcd585-68cd-44f3-b770-be3176eb0fd7
Pallesen, Jesper
4c823bd4-51f5-4b71-a1d4-ae9c1668ad78
Weiner, David B.
177ccd35-7ae1-40a3-b0f4-c984be75612b
Kulp, Daniel W.
3f4e260a-84f2-4140-b557-9bc3cb0947e7

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.

Text
1-s2.0-S2211124722000298-main - Version of Record
Available under License Creative Commons Attribution Non-commercial No Derivatives.
Download (5MB)

More information

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: 06 Jun 2024 01:59

Export record

Altmetrics

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Library staff additional information
Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×