Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences

Autores
Mareze, Vania Aparecida; Cristina, Borio; Bilen, Marcos Fabian; Fleith, Renata; Mirazo, Santiago; Santos Mansur, Daniel; Bruña Romero, Oscar; Arbiza, Juan; Mario Enrique, Lozano
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Two new vaccine candidates against dengue virus (DENV) infection were generated by fusing the coding sequences of the self-budding Z protein from Junin virus (Z-JUNV) to those of two cryptic peptides (Z/DENV-P1 and Z/DENV-P2) conserved on the envelope protein of all serotypes of DENV. The capacity of these chimeras to generate virus-like particles (VLPs) and to induce virus-neutralizing antibodies in mice was determined. First, recombinant proteins that displayed reactivity with a Z-JUNV-specific serum by immunofluorescence were detected in HEK-293 cells transfected with each of the two plasmids and VLP formation was also observed by transmission electron microscopy. Next, we determined the presence of antibodies against the envelope peptides of DENV in the sera of immunized C57BL/6 mice. Results showed that those animals that received Z/DENV-P2 DNA coding sequences followed by a boost with DENV-P2 synthetic peptides elicited significant specific antibody titers (≥6.400). Finally, DENV plaque-reduction neutralization tests (PRNT) were performed. Although no significant protective effect was observed when using sera of Z/DENV-P1-immunized animals, antibodies raised against vaccine candidate Z/DENV-P2 (diluted 1:320) were able to reduce in over 50 % the number of viral plaques generated by infectious DENV particles. This reduction was comparable to that of the 4G2 DENV-specific monoclonal cross-reactive (all serotypes) neutralizing antibody. We conclude that Z-JUNV-VLP is a valid carrier to induce antibody-mediated immune responses in mice and that Z/DENV-P2 is not only immunogenic but also protective in vitro against infection of cells with DENV, deserving further studies. On the other side, DENV´s fusion peptide-derived chimera Z/DENV-P1 did not display similar protective properties
Fil: Mareze, Vania Aparecida. 1UNIVERSIDADE FEDERAL DE SANTA CATARINA;
Fil: Cristina, Borio. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina
Fil: Bilen, Marcos Fabian. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina
Fil: Fleith, Renata. Universidade Federal Da Santa Catarina; Brasil
Fil: Mirazo, Santiago. Universidad de la Republica; Uruguay
Fil: Santos Mansur, Daniel. Universidade Federal Da Santa Catarina; Brasil
Fil: Bruña Romero, Oscar. Universidade Federal Da Santa Catarina; Brasil
Fil: Arbiza, Juan. Universidad de la Republica; Uruguay
Fil: Mario Enrique, Lozano. Universidad Nacional de Quilmes; Argentina
Materia
Vlps
Junin
Dengue
Vaccine
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/3815
Acceder
id CONICETDig_88470a563c9f5da98a456dcaa22317d6
oai_identifier_str oai:ri.conicet.gov.ar:11336/3815
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequencesMareze, Vania AparecidaCristina, BorioBilen, Marcos FabianFleith, RenataMirazo, SantiagoSantos Mansur, DanielBruña Romero, OscarArbiza, JuanMario Enrique, LozanoVlpsJuninDengueVaccinehttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Two new vaccine candidates against dengue virus (DENV) infection were generated by fusing the coding sequences of the self-budding Z protein from Junin virus (Z-JUNV) to those of two cryptic peptides (Z/DENV-P1 and Z/DENV-P2) conserved on the envelope protein of all serotypes of DENV. The capacity of these chimeras to generate virus-like particles (VLPs) and to induce virus-neutralizing antibodies in mice was determined. First, recombinant proteins that displayed reactivity with a Z-JUNV-specific serum by immunofluorescence were detected in HEK-293 cells transfected with each of the two plasmids and VLP formation was also observed by transmission electron microscopy. Next, we determined the presence of antibodies against the envelope peptides of DENV in the sera of immunized C57BL/6 mice. Results showed that those animals that received Z/DENV-P2 DNA coding sequences followed by a boost with DENV-P2 synthetic peptides elicited significant specific antibody titers (≥6.400). Finally, DENV plaque-reduction neutralization tests (PRNT) were performed. Although no significant protective effect was observed when using sera of Z/DENV-P1-immunized animals, antibodies raised against vaccine candidate Z/DENV-P2 (diluted 1:320) were able to reduce in over 50 % the number of viral plaques generated by infectious DENV particles. This reduction was comparable to that of the 4G2 DENV-specific monoclonal cross-reactive (all serotypes) neutralizing antibody. We conclude that Z-JUNV-VLP is a valid carrier to induce antibody-mediated immune responses in mice and that Z/DENV-P2 is not only immunogenic but also protective in vitro against infection of cells with DENV, deserving further studies. On the other side, DENV´s fusion peptide-derived chimera Z/DENV-P1 did not display similar protective propertiesFil: Mareze, Vania Aparecida. 1UNIVERSIDADE FEDERAL DE SANTA CATARINA;Fil: Cristina, Borio. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; ArgentinaFil: Bilen, Marcos Fabian. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; ArgentinaFil: Fleith, Renata. Universidade Federal Da Santa Catarina; BrasilFil: Mirazo, Santiago. Universidad de la Republica; UruguayFil: Santos Mansur, Daniel. Universidade Federal Da Santa Catarina; BrasilFil: Bruña Romero, Oscar. Universidade Federal Da Santa Catarina; BrasilFil: Arbiza, Juan. Universidad de la Republica; UruguayFil: Mario Enrique, Lozano. Universidad Nacional de Quilmes; ArgentinaSpringer2015-09-19info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3815Mareze, Vania Aparecida; Cristina, Borio; Bilen, Marcos Fabian; Fleith, Renata; Mirazo, Santiago; et al.; Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences; Springer; Applied Microbiology And Biotechnology; 19-9-20150175-7598enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1007/s00253-015-6973-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:34:47Zoai:ri.conicet.gov.ar:11336/3815instacron: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:34982025-09-29 10:34:47.568CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
title Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
spellingShingle Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
Mareze, Vania Aparecida
Vlps
Junin
Dengue
Vaccine
title_short Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
title_full Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
title_fullStr Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
title_full_unstemmed Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
title_sort Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences
dc.creator.none.fl_str_mv Mareze, Vania Aparecida
Cristina, Borio
Bilen, Marcos Fabian
Fleith, Renata
Mirazo, Santiago
Santos Mansur, Daniel
Bruña Romero, Oscar
Arbiza, Juan
Mario Enrique, Lozano
author Mareze, Vania Aparecida
author_facet Mareze, Vania Aparecida
Cristina, Borio
Bilen, Marcos Fabian
Fleith, Renata
Mirazo, Santiago
Santos Mansur, Daniel
Bruña Romero, Oscar
Arbiza, Juan
Mario Enrique, Lozano
author_role author
author2 Cristina, Borio
Bilen, Marcos Fabian
Fleith, Renata
Mirazo, Santiago
Santos Mansur, Daniel
Bruña Romero, Oscar
Arbiza, Juan
Mario Enrique, Lozano
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Vlps
Junin
Dengue
Vaccine
topic Vlps
Junin
Dengue
Vaccine
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Two new vaccine candidates against dengue virus (DENV) infection were generated by fusing the coding sequences of the self-budding Z protein from Junin virus (Z-JUNV) to those of two cryptic peptides (Z/DENV-P1 and Z/DENV-P2) conserved on the envelope protein of all serotypes of DENV. The capacity of these chimeras to generate virus-like particles (VLPs) and to induce virus-neutralizing antibodies in mice was determined. First, recombinant proteins that displayed reactivity with a Z-JUNV-specific serum by immunofluorescence were detected in HEK-293 cells transfected with each of the two plasmids and VLP formation was also observed by transmission electron microscopy. Next, we determined the presence of antibodies against the envelope peptides of DENV in the sera of immunized C57BL/6 mice. Results showed that those animals that received Z/DENV-P2 DNA coding sequences followed by a boost with DENV-P2 synthetic peptides elicited significant specific antibody titers (≥6.400). Finally, DENV plaque-reduction neutralization tests (PRNT) were performed. Although no significant protective effect was observed when using sera of Z/DENV-P1-immunized animals, antibodies raised against vaccine candidate Z/DENV-P2 (diluted 1:320) were able to reduce in over 50 % the number of viral plaques generated by infectious DENV particles. This reduction was comparable to that of the 4G2 DENV-specific monoclonal cross-reactive (all serotypes) neutralizing antibody. We conclude that Z-JUNV-VLP is a valid carrier to induce antibody-mediated immune responses in mice and that Z/DENV-P2 is not only immunogenic but also protective in vitro against infection of cells with DENV, deserving further studies. On the other side, DENV´s fusion peptide-derived chimera Z/DENV-P1 did not display similar protective properties
Fil: Mareze, Vania Aparecida. 1UNIVERSIDADE FEDERAL DE SANTA CATARINA;
Fil: Cristina, Borio. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina
Fil: Bilen, Marcos Fabian. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina
Fil: Fleith, Renata. Universidade Federal Da Santa Catarina; Brasil
Fil: Mirazo, Santiago. Universidad de la Republica; Uruguay
Fil: Santos Mansur, Daniel. Universidade Federal Da Santa Catarina; Brasil
Fil: Bruña Romero, Oscar. Universidade Federal Da Santa Catarina; Brasil
Fil: Arbiza, Juan. Universidad de la Republica; Uruguay
Fil: Mario Enrique, Lozano. Universidad Nacional de Quilmes; Argentina
description Two new vaccine candidates against dengue virus (DENV) infection were generated by fusing the coding sequences of the self-budding Z protein from Junin virus (Z-JUNV) to those of two cryptic peptides (Z/DENV-P1 and Z/DENV-P2) conserved on the envelope protein of all serotypes of DENV. The capacity of these chimeras to generate virus-like particles (VLPs) and to induce virus-neutralizing antibodies in mice was determined. First, recombinant proteins that displayed reactivity with a Z-JUNV-specific serum by immunofluorescence were detected in HEK-293 cells transfected with each of the two plasmids and VLP formation was also observed by transmission electron microscopy. Next, we determined the presence of antibodies against the envelope peptides of DENV in the sera of immunized C57BL/6 mice. Results showed that those animals that received Z/DENV-P2 DNA coding sequences followed by a boost with DENV-P2 synthetic peptides elicited significant specific antibody titers (≥6.400). Finally, DENV plaque-reduction neutralization tests (PRNT) were performed. Although no significant protective effect was observed when using sera of Z/DENV-P1-immunized animals, antibodies raised against vaccine candidate Z/DENV-P2 (diluted 1:320) were able to reduce in over 50 % the number of viral plaques generated by infectious DENV particles. This reduction was comparable to that of the 4G2 DENV-specific monoclonal cross-reactive (all serotypes) neutralizing antibody. We conclude that Z-JUNV-VLP is a valid carrier to induce antibody-mediated immune responses in mice and that Z/DENV-P2 is not only immunogenic but also protective in vitro against infection of cells with DENV, deserving further studies. On the other side, DENV´s fusion peptide-derived chimera Z/DENV-P1 did not display similar protective properties
publishDate 2015
dc.date.none.fl_str_mv 2015-09-19
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/11336/3815
Mareze, Vania Aparecida; Cristina, Borio; Bilen, Marcos Fabian; Fleith, Renata; Mirazo, Santiago; et al.; Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences; Springer; Applied Microbiology And Biotechnology; 19-9-2015
0175-7598
url http://hdl.handle.net/11336/3815
identifier_str_mv Mareze, Vania Aparecida; Cristina, Borio; Bilen, Marcos Fabian; Fleith, Renata; Mirazo, Santiago; et al.; Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences; Springer; Applied Microbiology And Biotechnology; 19-9-2015
0175-7598
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00253-015-6973-7
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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
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score 13.070432

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