Cargando…

Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy

Dengue virus (DENV) is the most important mosquito-borne viral infection in humans. In recent years, the number of cases and outbreaks has dramatically increased worldwide. While vaccines are being developed, none are currently available that provide balanced protection against all DENV serotypes. A...

Descripción completa

Detalles Bibliográficos
Autores principales: Flingai, Seleeke, Plummer, Emily M., Patel, Ami, Shresta, Sujan, Mendoza, Janess M., Broderick, Kate E., Sardesai, Niranjan Y., Muthumani, Kar, Weiner, David B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518257/
https://www.ncbi.nlm.nih.gov/pubmed/26220099
http://dx.doi.org/10.1038/srep12616
_version_ 1782383314885148672
author Flingai, Seleeke
Plummer, Emily M.
Patel, Ami
Shresta, Sujan
Mendoza, Janess M.
Broderick, Kate E.
Sardesai, Niranjan Y.
Muthumani, Kar
Weiner, David B.
author_facet Flingai, Seleeke
Plummer, Emily M.
Patel, Ami
Shresta, Sujan
Mendoza, Janess M.
Broderick, Kate E.
Sardesai, Niranjan Y.
Muthumani, Kar
Weiner, David B.
author_sort Flingai, Seleeke
collection PubMed
description Dengue virus (DENV) is the most important mosquito-borne viral infection in humans. In recent years, the number of cases and outbreaks has dramatically increased worldwide. While vaccines are being developed, none are currently available that provide balanced protection against all DENV serotypes. Advances in human antibody isolation have uncovered DENV neutralizing antibodies (nAbs) that are capable of preventing infection from multiple serotypes. Yet delivering monoclonal antibodies using conventional methods is impractical due to high costs. Engineering novel methods of delivering monoclonal antibodies could tip the scale in the fight against DENV. Here we demonstrate that simple intramuscular delivery by electroporation of synthetic DNA plasmids engineered to express modified human nAbs against multiple DENV serotypes confers protection against DENV disease and prevents antibody-dependent enhancement (ADE) of disease in mice. This synthetic nucleic acid antibody prophylaxis/immunotherapy approach may have important applications in the fight against infectious disease.
format Online
Article
Text
id pubmed-4518257
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-45182572015-08-06 Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy Flingai, Seleeke Plummer, Emily M. Patel, Ami Shresta, Sujan Mendoza, Janess M. Broderick, Kate E. Sardesai, Niranjan Y. Muthumani, Kar Weiner, David B. Sci Rep Article Dengue virus (DENV) is the most important mosquito-borne viral infection in humans. In recent years, the number of cases and outbreaks has dramatically increased worldwide. While vaccines are being developed, none are currently available that provide balanced protection against all DENV serotypes. Advances in human antibody isolation have uncovered DENV neutralizing antibodies (nAbs) that are capable of preventing infection from multiple serotypes. Yet delivering monoclonal antibodies using conventional methods is impractical due to high costs. Engineering novel methods of delivering monoclonal antibodies could tip the scale in the fight against DENV. Here we demonstrate that simple intramuscular delivery by electroporation of synthetic DNA plasmids engineered to express modified human nAbs against multiple DENV serotypes confers protection against DENV disease and prevents antibody-dependent enhancement (ADE) of disease in mice. This synthetic nucleic acid antibody prophylaxis/immunotherapy approach may have important applications in the fight against infectious disease. Nature Publishing Group 2015-07-29 /pmc/articles/PMC4518257/ /pubmed/26220099 http://dx.doi.org/10.1038/srep12616 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Flingai, Seleeke
Plummer, Emily M.
Patel, Ami
Shresta, Sujan
Mendoza, Janess M.
Broderick, Kate E.
Sardesai, Niranjan Y.
Muthumani, Kar
Weiner, David B.
Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy
title Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy
title_full Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy
title_fullStr Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy
title_full_unstemmed Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy
title_short Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy
title_sort protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518257/
https://www.ncbi.nlm.nih.gov/pubmed/26220099
http://dx.doi.org/10.1038/srep12616
work_keys_str_mv AT flingaiseleeke protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT plummeremilym protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT patelami protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT shrestasujan protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT mendozajanessm protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT broderickkatee protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT sardesainiranjany protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT muthumanikar protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy
AT weinerdavidb protectionagainstdenguediseasebysyntheticnucleicacidantibodyprophylaxisimmunotherapy