Cargando…

Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model

Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respirato...

Descripción completa

Detalles Bibliográficos
Autores principales: Patel, DR, Minns, AM, Sim, DG, Field, CJ, Kerr, AE, Heinly, T, Luley, EH, Rossi, R.M., Bator, C., Moustafa, I.M., Hafenstein, SL, Lindner, SE, Sutton, TC
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628200/
https://www.ncbi.nlm.nih.gov/pubmed/36324809
http://dx.doi.org/10.1101/2022.10.27.514054
_version_ 1784823144357298176
author Patel, DR
Minns, AM
Sim, DG
Field, CJ
Kerr, AE
Heinly, T
Luley, EH
Rossi, R.M.
Bator, C.
Moustafa, I.M.
Hafenstein, SL
Lindner, SE
Sutton, TC
author_facet Patel, DR
Minns, AM
Sim, DG
Field, CJ
Kerr, AE
Heinly, T
Luley, EH
Rossi, R.M.
Bator, C.
Moustafa, I.M.
Hafenstein, SL
Lindner, SE
Sutton, TC
author_sort Patel, DR
collection PubMed
description Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the “gold-standard” preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.
format Online
Article
Text
id pubmed-9628200
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Cold Spring Harbor Laboratory
record_format MEDLINE/PubMed
spelling pubmed-96282002022-12-15 Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model Patel, DR Minns, AM Sim, DG Field, CJ Kerr, AE Heinly, T Luley, EH Rossi, R.M. Bator, C. Moustafa, I.M. Hafenstein, SL Lindner, SE Sutton, TC bioRxiv Article Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the “gold-standard” preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens. Cold Spring Harbor Laboratory 2022-12-14 /pmc/articles/PMC9628200/ /pubmed/36324809 http://dx.doi.org/10.1101/2022.10.27.514054 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Patel, DR
Minns, AM
Sim, DG
Field, CJ
Kerr, AE
Heinly, T
Luley, EH
Rossi, R.M.
Bator, C.
Moustafa, I.M.
Hafenstein, SL
Lindner, SE
Sutton, TC
Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
title Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
title_full Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
title_fullStr Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
title_full_unstemmed Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
title_short Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
title_sort intranasal sars-cov-2 rbd decorated nanoparticle vaccine enhances viral clearance in the syrian hamster model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628200/
https://www.ncbi.nlm.nih.gov/pubmed/36324809
http://dx.doi.org/10.1101/2022.10.27.514054
work_keys_str_mv AT pateldr intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT minnsam intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT simdg intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT fieldcj intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT kerrae intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT heinlyt intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT luleyeh intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT rossirm intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT batorc intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT moustafaim intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT hafensteinsl intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT lindnerse intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel
AT suttontc intranasalsarscov2rbddecoratednanoparticlevaccineenhancesviralclearanceinthesyrianhamstermodel