Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus

New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host make...

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Autores: Roman Sosa, Gleyder, Leske, Anne, Ficht, Xenia, Dau, Tung Huy, Holzerland, Julia, Hoenen, Thomas, Beer, Martin, Kammerer, Robert, Schirmbeck, Reinhold, Rey, Felix A., Cordo, Sandra Myriam, Groseth, Allison
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/213629
Acceso en línea:http://hdl.handle.net/11336/213629
Access Level:acceso abierto
Palabra clave:ARENAVIRUS
GLYCOPROTEIN
GP1
IMMUNE RESPONSE
JUNÍN VIRUS
NEUTRALIZING ANTIBODIES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
id AR_64a06b67affc84792ff165e7fb966d8c
oai_identifier_str oai:ri.conicet.gov.ar:11336/213629
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
title Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
spellingShingle Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
Roman Sosa, Gleyder
ARENAVIRUS
GLYCOPROTEIN
GP1
IMMUNE RESPONSE
JUNÍN VIRUS
NEUTRALIZING ANTIBODIES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
title_full Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
title_fullStr Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
title_full_unstemmed Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
title_sort Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus
dc.creator.none.fl_str_mv Roman Sosa, Gleyder
Leske, Anne
Ficht, Xenia
Dau, Tung Huy
Holzerland, Julia
Hoenen, Thomas
Beer, Martin
Kammerer, Robert
Schirmbeck, Reinhold
Rey, Felix A.
Cordo, Sandra Myriam
Groseth, Allison
author Roman Sosa, Gleyder
author_facet Roman Sosa, Gleyder
Leske, Anne
Ficht, Xenia
Dau, Tung Huy
Holzerland, Julia
Hoenen, Thomas
Beer, Martin
Kammerer, Robert
Schirmbeck, Reinhold
Rey, Felix A.
Cordo, Sandra Myriam
Groseth, Allison
author_role author
author2 Leske, Anne
Ficht, Xenia
Dau, Tung Huy
Holzerland, Julia
Hoenen, Thomas
Beer, Martin
Kammerer, Robert
Schirmbeck, Reinhold
Rey, Felix A.
Cordo, Sandra Myriam
Groseth, Allison
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ARENAVIRUS
GLYCOPROTEIN
GP1
IMMUNE RESPONSE
JUNÍN VIRUS
NEUTRALIZING ANTIBODIES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic ARENAVIRUS
GLYCOPROTEIN
GP1
IMMUNE RESPONSE
JUNÍN VIRUS
NEUTRALIZING ANTIBODIES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host makes it difficult to control the disease, and currently passive immunization with high-titer neutralizing antibody-containing plasma from convalescent patients is the only specific therapy. However, dwindling supplies of naturally available convalescent plasma, and challenges in developing similar resources for other closely related viruses, have made the development of alternative antibody-based therapeutic approaches of critical importance. In this study, we sought to induce a neutralizing antibody response in rabbits against the receptor-binding subunit of the viral glycoprotein, GP1, and the specific peptide sequences in GP1 involved in cellular receptor contacts. While these specific receptor-interacting peptides did not efficiently induce the production of neutralizing antibodies when delivered as a particulate antigen (as part of hepatitis B virus core-like particles), we showed that recombinant JUNV GP1 purified from transfected mammalian cells induced virus-neutralizing antibodies at high titers in rabbits. Further, neutralization was observed across a range of unrelated JUNV strains, a feature that is critical for effectiveness in the field. These results underscore the potential of GP1 alone to induce a potent neutralizing antibody response and highlight the importance of epitope presentation. In addition, effective virus neutralization by rabbit antibodies supports the potential applicability of this species for the future development of immunotherapeutics (e.g., based on humanized monoclonal antibodies). Such information can be applied in the design of vaccines and immunogens for both prevention and specific therapies against this and likely also other closely related pathogenic New World arenaviruses.
publishDate 2022
dc.date.none.fl_str_mv 2022-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/213629
Roman Sosa, Gleyder; Leske, Anne; Ficht, Xenia; Dau, Tung Huy; Holzerland, Julia; et al.; Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus; MDPI; Vaccines; 10; 2; 2-2022; 1-19
2076-393X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/213629
identifier_str_mv Roman Sosa, Gleyder; Leske, Anne; Ficht, Xenia; Dau, Tung Huy; Holzerland, Julia; et al.; Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus; MDPI; Vaccines; 10; 2; 2-2022; 1-19
2076-393X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/vaccines10020173
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799194688704479232
spelling Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín VirusRoman Sosa, GleyderLeske, AnneFicht, XeniaDau, Tung HuyHolzerland, JuliaHoenen, ThomasBeer, MartinKammerer, RobertSchirmbeck, ReinholdRey, Felix A.Cordo, Sandra MyriamGroseth, AllisonARENAVIRUSGLYCOPROTEINGP1IMMUNE RESPONSEJUNÍN VIRUSNEUTRALIZING ANTIBODIEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host makes it difficult to control the disease, and currently passive immunization with high-titer neutralizing antibody-containing plasma from convalescent patients is the only specific therapy. However, dwindling supplies of naturally available convalescent plasma, and challenges in developing similar resources for other closely related viruses, have made the development of alternative antibody-based therapeutic approaches of critical importance. In this study, we sought to induce a neutralizing antibody response in rabbits against the receptor-binding subunit of the viral glycoprotein, GP1, and the specific peptide sequences in GP1 involved in cellular receptor contacts. While these specific receptor-interacting peptides did not efficiently induce the production of neutralizing antibodies when delivered as a particulate antigen (as part of hepatitis B virus core-like particles), we showed that recombinant JUNV GP1 purified from transfected mammalian cells induced virus-neutralizing antibodies at high titers in rabbits. Further, neutralization was observed across a range of unrelated JUNV strains, a feature that is critical for effectiveness in the field. These results underscore the potential of GP1 alone to induce a potent neutralizing antibody response and highlight the importance of epitope presentation. In addition, effective virus neutralization by rabbit antibodies supports the potential applicability of this species for the future development of immunotherapeutics (e.g., based on humanized monoclonal antibodies). Such information can be applied in the design of vaccines and immunogens for both prevention and specific therapies against this and likely also other closely related pathogenic New World arenaviruses.Fil: Roman Sosa, Gleyder. Ulm University Hospital; AlemaniaFil: Leske, Anne. Friedrich-Loeffler-Institut; AlemaniaFil: Ficht, Xenia. Ulm University Hospital; AlemaniaFil: Dau, Tung Huy. Friedrich-Loeffler-Institut; AlemaniaFil: Holzerland, Julia. Friedrich-Loeffler-Institut; AlemaniaFil: Hoenen, Thomas. Friedrich-Loeffler-Institut; AlemaniaFil: Beer, Martin. Friedrich-Loeffler-Institut; AlemaniaFil: Kammerer, Robert. Friedrich-Loeffler-Institut; AlemaniaFil: Schirmbeck, Reinhold. Friedrich-Loeffler-Institut; AlemaniaFil: Rey, Felix A.. Friedrich-Loeffler-Institut; AlemaniaFil: Cordo, Sandra Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Groseth, Allison. Friedrich-Loeffler-Institut; AlemaniaMDPI2022-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/213629Roman Sosa, Gleyder; Leske, Anne; Ficht, Xenia; Dau, Tung Huy; Holzerland, Julia; et al.; Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus; MDPI; Vaccines; 10; 2; 2-2022; 1-192076-393XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/vaccines10020173info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:34:15Zoai:ri.conicet.gov.ar:11336/213629instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:34:15.829CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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