Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant

Detalhes bibliográficos
Autor(a) principal: Amorim, Jaime Henrique
Data de Publicação: 2012
Outros Autores: Diniz, Mariana Oliveira, Cariri, Francisco A. M. O., Rodrigues, Juliana Falcão, Bizerra, Raíza Sales Pereira, Gonçalves, Antônio J. S., Alves, Ada Maria de Barcelos, Ferreira, Luís Carlos de Souza
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/15379
Resumo: Universidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.
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spelling Amorim, Jaime HenriqueDiniz, Mariana OliveiraCariri, Francisco A. M. O.Rodrigues, Juliana FalcãoBizerra, Raíza Sales PereiraGonçalves, Antônio J. S.Alves, Ada Maria de BarcelosFerreira, Luís Carlos de Souza2016-08-25T10:48:19Z2016-08-25T10:48:19Z2012AMORIM, Jaime Henrique; et al. Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant. Vaccine.v.30, p.837-845, 2012.0264-410Xhttps://www.arca.fiocruz.br/handle/icict/1537910.1016/j.vaccine.2011.12.034engElsevierVírus da DengueAdjuvantesVacinasproteína NS1Dengue virusNS1proteinHeat-labile toxinAdjuvantsVaccinesProtective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvantinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.Universidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.Universidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.Universidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.Universidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil / Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.The dengue virus non-structural 1 (NS1) protein contributes to evasion of host immune defenses and represents a target for immune responses. Evidences generated in experimental models, as well as the immune responses elicited by infected individuals, showed that induction of anti-NS1 immunity correlates with protective immunity but may also result in the generation of cross-reactive antibodies that recognize platelets and proteins involved in the coagulation cascade. In the present work, we evaluated the immune responses, protection to type 2 dengue virus (DENV2) challenges and safety parameters in BALB/c mice vaccinated with a recombinant NS1 protein in combination with three different adjuvants: aluminum hydroxide (alum), Freund's adjuvant (FA) or a genetically detoxified derivative of the heat-labile toxin (LT(G33D)), originally produced by some enterotoxigenic Escherichia coli (ETEC) strains. Mice were subcutaneously (s.c.) immunized with different vaccine formulations and the induced NS1-specific responses, including serum antibodies and T cell responses, were measured. Mice were also subjected to lethal challenges with the DENV2 NGC strain. The results showed that maximal protective immunity (50%) was achieved in mice vaccinated with NS1 in combination with LT(G33D). Analyses of the NS1-specific immune responses showed that the anti-virus protection correlated mainly with the serum anti-NS1 antibody responses including higher avidity to the target antigen. Mice immunized with LT(G33D) elicited a prevailing IgG2a subclass response and generated antibodies with stronger affinity to the antigen than those generated in mice immunized with the other vaccine formulations. The vaccine formulations were also evaluated regarding induction of deleterious side effects and, in contrast to mice immunized with the FA-adjuvanted vaccine, no significant hepatic damage or enhanced C-reactive protein levels were detected in mice immunized with NS1 and LT(G33D.) Similarly, no detectable alterations in bleeding time and hematological parameters were detected in mice vaccinated with NS1 and LT(G33D). Altogether, these results indicate that the combination of a purified recombinant NS1 and a nontoxic LT derivative is a promising alternative for the generation of safe and effective protein-based anti-dengue vaccine.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/15379/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALada_alves_etal_IOC_2012.pdfada_alves_etal_IOC_2012.pdfapplication/pdf817391https://www.arca.fiocruz.br/bitstream/icict/15379/2/ada_alves_etal_IOC_2012.pdf7aa356e7eacf65a8a014b1d9c58c833aMD52TEXTada_alves_etal_IOC_2012.pdf.txtada_alves_etal_IOC_2012.pdf.txtExtracted texttext/plain54937https://www.arca.fiocruz.br/bitstream/icict/15379/3/ada_alves_etal_IOC_2012.pdf.txt5926cfc7570b69ce8e8b59aa2009edd3MD53icict/153792018-04-02 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dc.title.pt_BR.fl_str_mv Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
title Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
spellingShingle Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
Amorim, Jaime Henrique
Vírus da Dengue
Adjuvantes
Vacinas
proteína NS1
Dengue virus
NS1protein
Heat-labile toxin
Adjuvants
Vaccines
title_short Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
title_full Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
title_fullStr Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
title_full_unstemmed Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
title_sort Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant
author Amorim, Jaime Henrique
author_facet Amorim, Jaime Henrique
Diniz, Mariana Oliveira
Cariri, Francisco A. M. O.
Rodrigues, Juliana Falcão
Bizerra, Raíza Sales Pereira
Gonçalves, Antônio J. S.
Alves, Ada Maria de Barcelos
Ferreira, Luís Carlos de Souza
author_role author
author2 Diniz, Mariana Oliveira
Cariri, Francisco A. M. O.
Rodrigues, Juliana Falcão
Bizerra, Raíza Sales Pereira
Gonçalves, Antônio J. S.
Alves, Ada Maria de Barcelos
Ferreira, Luís Carlos de Souza
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Amorim, Jaime Henrique
Diniz, Mariana Oliveira
Cariri, Francisco A. M. O.
Rodrigues, Juliana Falcão
Bizerra, Raíza Sales Pereira
Gonçalves, Antônio J. S.
Alves, Ada Maria de Barcelos
Ferreira, Luís Carlos de Souza
dc.subject.other.pt_BR.fl_str_mv Vírus da Dengue
Adjuvantes
Vacinas
proteína NS1
topic Vírus da Dengue
Adjuvantes
Vacinas
proteína NS1
Dengue virus
NS1protein
Heat-labile toxin
Adjuvants
Vaccines
dc.subject.en.pt_BR.fl_str_mv Dengue virus
NS1protein
Heat-labile toxin
Adjuvants
Vaccines
description Universidade de São Paulo. Departamento de Microbiologia. Laboratório de Desenvolvimento de Vacinas. São Paulo, SP, Brasil.
publishDate 2012
dc.date.issued.fl_str_mv 2012
dc.date.accessioned.fl_str_mv 2016-08-25T10:48:19Z
dc.date.available.fl_str_mv 2016-08-25T10:48:19Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv AMORIM, Jaime Henrique; et al. Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant. Vaccine.v.30, p.837-845, 2012.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/15379
dc.identifier.issn.pt_BR.fl_str_mv 0264-410X
dc.identifier.doi.none.fl_str_mv 10.1016/j.vaccine.2011.12.034
identifier_str_mv AMORIM, Jaime Henrique; et al. Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant. Vaccine.v.30, p.837-845, 2012.
0264-410X
10.1016/j.vaccine.2011.12.034
url https://www.arca.fiocruz.br/handle/icict/15379
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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