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Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge

Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the...

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Autores principales: Henriques, Hugo R., Rampazo, Eline V., Gonçalves, Antonio J. S., Vicentin, Elaine C. M., Amorim, Jaime H., Panatieri, Raquel H., Amorim, Kelly N. S., Yamamoto, Marcio M., Ferreira, Luís C. S., Alves, Ada M. B., Boscardin, Silvia B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715404/
https://www.ncbi.nlm.nih.gov/pubmed/23875054
http://dx.doi.org/10.1371/journal.pntd.0002330
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author Henriques, Hugo R.
Rampazo, Eline V.
Gonçalves, Antonio J. S.
Vicentin, Elaine C. M.
Amorim, Jaime H.
Panatieri, Raquel H.
Amorim, Kelly N. S.
Yamamoto, Marcio M.
Ferreira, Luís C. S.
Alves, Ada M. B.
Boscardin, Silvia B.
author_facet Henriques, Hugo R.
Rampazo, Eline V.
Gonçalves, Antonio J. S.
Vicentin, Elaine C. M.
Amorim, Jaime H.
Panatieri, Raquel H.
Amorim, Kelly N. S.
Yamamoto, Marcio M.
Ferreira, Luís C. S.
Alves, Ada M. B.
Boscardin, Silvia B.
author_sort Henriques, Hugo R.
collection PubMed
description Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1). In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs) are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb) directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (αDEC205 and αDCIR2) to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Protection was partially mediated by CD4(+) and CD8(+) T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+) DC population with poly (I:C) opens perspectives for dengue vaccine development.
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spelling pubmed-37154042013-07-19 Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge Henriques, Hugo R. Rampazo, Eline V. Gonçalves, Antonio J. S. Vicentin, Elaine C. M. Amorim, Jaime H. Panatieri, Raquel H. Amorim, Kelly N. S. Yamamoto, Marcio M. Ferreira, Luís C. S. Alves, Ada M. B. Boscardin, Silvia B. PLoS Negl Trop Dis Research Article Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1). In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs) are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb) directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (αDEC205 and αDCIR2) to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Protection was partially mediated by CD4(+) and CD8(+) T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+) DC population with poly (I:C) opens perspectives for dengue vaccine development. Public Library of Science 2013-07-18 /pmc/articles/PMC3715404/ /pubmed/23875054 http://dx.doi.org/10.1371/journal.pntd.0002330 Text en © 2013 Henriques et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Henriques, Hugo R.
Rampazo, Eline V.
Gonçalves, Antonio J. S.
Vicentin, Elaine C. M.
Amorim, Jaime H.
Panatieri, Raquel H.
Amorim, Kelly N. S.
Yamamoto, Marcio M.
Ferreira, Luís C. S.
Alves, Ada M. B.
Boscardin, Silvia B.
Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge
title Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge
title_full Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge
title_fullStr Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge
title_full_unstemmed Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge
title_short Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge
title_sort targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715404/
https://www.ncbi.nlm.nih.gov/pubmed/23875054
http://dx.doi.org/10.1371/journal.pntd.0002330
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