Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection

Slow-antigen release vaccination systems aim to replicate the prolonged antigen exposure occurring during natural viral infections, which usually last for days or weeks. We have developed a Zn-assisted, self-organizing protein material at the microscale, inspired by the granular depots for protein h...

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Autores: Parladé, Eloi, Tarrés Freixas, Ferran, Favaro, Marianna T.P., Lascorz, Jara, Marquez-Matínez, Merce, Mendoza, Rosa, Corchero, José Luís, Cantero Portillo, Guillermo, Roca, Núria, Pérez, Mónica, Ferrer-Miralles, Neus, Vazquez, Esther, Segalés, Joaquim, Vergara-Alert, Júlia, Villaverde, Antonio
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Institut de Recerca i Tecnologia Agroalimentàries (IRTA)
Repositorio:IRTA Pubpro. Open Digital Archive
OAI Identifier:oai:repositori.irta.cat:20.500.12327/3744
Acceso en línea:http://hdl.handle.net/20.500.12327/3744
https://doi.org/10.1016/j.jddst.2025.106813
Access Level:acceso abierto
Palabra clave:619
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oai_identifier_str oai:repositori.irta.cat:20.500.12327/3744
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
title Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
spellingShingle Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
Parladé, Eloi
619
title_short Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
title_full Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
title_fullStr Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
title_full_unstemmed Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
title_sort Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infection
dc.creator.none.fl_str_mv Parladé, Eloi
Tarrés Freixas, Ferran
Favaro, Marianna T.P.
Lascorz, Jara
Marquez-Matínez, Merce
Mendoza, Rosa
Corchero, José Luís
Cantero Portillo, Guillermo
Roca, Núria
Pérez, Mónica
Ferrer-Miralles, Neus
Vazquez, Esther
Segalés, Joaquim
Vergara-Alert, Júlia
Villaverde, Antonio
author Parladé, Eloi
author_facet Parladé, Eloi
Tarrés Freixas, Ferran
Favaro, Marianna T.P.
Lascorz, Jara
Marquez-Matínez, Merce
Mendoza, Rosa
Corchero, José Luís
Cantero Portillo, Guillermo
Roca, Núria
Pérez, Mónica
Ferrer-Miralles, Neus
Vazquez, Esther
Segalés, Joaquim
Vergara-Alert, Júlia
Villaverde, Antonio
author_role author
author2 Tarrés Freixas, Ferran
Favaro, Marianna T.P.
Lascorz, Jara
Marquez-Matínez, Merce
Mendoza, Rosa
Corchero, José Luís
Cantero Portillo, Guillermo
Roca, Núria
Pérez, Mónica
Ferrer-Miralles, Neus
Vazquez, Esther
Segalés, Joaquim
Vergara-Alert, Júlia
Villaverde, Antonio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Producció Animal
Sanitat Animal
dc.subject.none.fl_str_mv 619
topic 619
description Slow-antigen release vaccination systems aim to replicate the prolonged antigen exposure occurring during natural viral infections, which usually last for days or weeks. We have developed a Zn-assisted, self-organizing protein material at the microscale, inspired by the granular depots for protein hormones, that slowly disassembles into functional building block polypeptides under physiological conditions. This endocrine-like platform acts as a dynamic protein depot for prolonged protein release. Having been validated in oncology, regenerative medicine, and in antimicrobial peptide delivery, it also shows promise for immune stimulation. Here, we evaluate, for the first time, whether such artificial secretory granules incorporating the SARS-CoV-2 Spike Receptor Binding Domain (RBD) can elicit a protective immune response against viral challenge in golden Syrian hamsters. The antigen, formulated as secretory granules, was administered in varying doses via intranasal or subcutaneous routes. While the formulations did not prevent infection, they enhanced viral clearance and mitigated body weight loss, particularly with subcutaneous administration. These effects, through the subcutaneous route, were achieved even in the absence of an adjuvant. Additionally, the granules triggered both antigen-specific humoral immunity and antigen-independent immunomodulatory effects, potentially linked to their amyloid-like structure. These findings demonstrate the dual mechanism of this platform, activating both adaptive and innate immune pathways, and its potential as a versatile, adjuvant-free system for enhancing immune responses against infectious diseases.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12327/3744
https://doi.org/10.1016/j.jddst.2025.106813
url http://hdl.handle.net/20.500.12327/3744
https://doi.org/10.1016/j.jddst.2025.106813
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Drug Delivery Science and Technology
MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-105416RB-I00/ES/ /
MICINN/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PDC2022-133858-I00/ES/ /
MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-116174RB-I00/ES/
MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/PID2019-107298RB-C22/ES/ NANOINGENIERIA APLICADA A SISTEMAS DE ADMINISTRACION EFICIENTE DE FARMACOS BASADOS EN LA DEFENSA DEL HUESPED POR VIA INTRANASAL/
CIBER/ /CB-06-01-0014/ES/ /
MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-116174RB-I00/ES/ /
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:IRTA Pubpro. Open Digital Archive
instname:Institut de Recerca i Tecnologia Agroalimentàries (IRTA)
instname_str Institut de Recerca i Tecnologia Agroalimentàries (IRTA)
reponame_str IRTA Pubpro. Open Digital Archive
collection IRTA Pubpro. Open Digital Archive
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Subcutaneous administration of an endocrine-mimetic, slow-release protein material reduces the severity of SARS-CoV-2 infectionParladé, EloiTarrés Freixas, FerranFavaro, Marianna T.P.Lascorz, JaraMarquez-Matínez, MerceMendoza, RosaCorchero, José LuísCantero Portillo, GuillermoRoca, NúriaPérez, MónicaFerrer-Miralles, NeusVazquez, EstherSegalés, JoaquimVergara-Alert, JúliaVillaverde, Antonio619Slow-antigen release vaccination systems aim to replicate the prolonged antigen exposure occurring during natural viral infections, which usually last for days or weeks. We have developed a Zn-assisted, self-organizing protein material at the microscale, inspired by the granular depots for protein hormones, that slowly disassembles into functional building block polypeptides under physiological conditions. This endocrine-like platform acts as a dynamic protein depot for prolonged protein release. Having been validated in oncology, regenerative medicine, and in antimicrobial peptide delivery, it also shows promise for immune stimulation. Here, we evaluate, for the first time, whether such artificial secretory granules incorporating the SARS-CoV-2 Spike Receptor Binding Domain (RBD) can elicit a protective immune response against viral challenge in golden Syrian hamsters. The antigen, formulated as secretory granules, was administered in varying doses via intranasal or subcutaneous routes. While the formulations did not prevent infection, they enhanced viral clearance and mitigated body weight loss, particularly with subcutaneous administration. These effects, through the subcutaneous route, were achieved even in the absence of an adjuvant. Additionally, the granules triggered both antigen-specific humoral immunity and antigen-independent immunomodulatory effects, potentially linked to their amyloid-like structure. These findings demonstrate the dual mechanism of this platform, activating both adaptive and innate immune pathways, and its potential as a versatile, adjuvant-free system for enhancing immune responses against infectious diseases.The project was mainly funded by AGAUR (grant number 2020PANDE00003) and CIBER-Consorcio Centro de Investigación Biomédica en Red- (grant number CB06/01/0014), through the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, within the intramural project NANOSARS (to E.P.). We also gratefully acknowledge the support from AEI for the development of multimeric recombinant drugs (grant numbers PID2019-105416RB-I00/AEI/10.13039/501100011033 and PDC2022-133858-I00 to E.V., PID2019-107298RB-C22/AEI/10.13039/501100011033 to N.F.-M., PID2020-116174RB-I00 to A.V. and PID2022-1368450 OB-10/AEI/10.13039/501100011033 to A.V. and E.V.). Our team also received support from AGAUR for our activities in drug design (grant number 2021SGR00092 to A.V.). Protein production was partially performed by the ICTS “NANBIOSIS”, more specifically by the Protein Production Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)/IBB, at the UAB (http://www.nanbiosis.es/portfolio/u1-protein-production-platform-ppp). IRTA is supported by CERCA Programme/Generalitat de Catalunya. The authors also acknowledge the invaluable assistance of the animal caretakers at the BSL3 facility at IRTA.info:eu-repo/semantics/publishedVersionElsevierProducció AnimalSanitat Animal202520252025info:eu-repo/semantics/article9application/pdfhttp://hdl.handle.net/20.500.12327/3744https://doi.org/10.1016/j.jddst.2025.106813reponame:IRTA Pubpro. Open Digital Archiveinstname:Institut de Recerca i Tecnologia Agroalimentàries (IRTA)InglésJournal of Drug Delivery Science and TechnologyMICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-105416RB-I00/ES/ /MICINN/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PDC2022-133858-I00/ES/ /MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-116174RB-I00/ES/MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/PID2019-107298RB-C22/ES/ NANOINGENIERIA APLICADA A SISTEMAS DE ADMINISTRACION EFICIENTE DE FARMACOS BASADOS EN LA DEFENSA DEL HUESPED POR VIA INTRANASAL/CIBER/ /CB-06-01-0014/ES/ /MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-116174RB-I00/ES/ /Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.irta.cat:20.500.12327/37442026-06-16T08:51:17Z
score 15.812455

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