Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses

Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses

The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses i...

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Main Authors: Jingjing Jiang, Stephanie J. Ramos, Preeti Bangalore, Dustin Elwood, Kathleen A. Cashman, Sagar B. Kudchodkar, Katherine Schultheis, Holly Pugh, Jewell Walters, Jared Tur, Jian Yan, Ami Patel, Kar Muthumani, Connie S. Schmaljohn, David B. Weiner, Laurent M. Humeau, Kate E. Broderick
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Viruses
Subjects:
DNA vaccine
Multivalent vaccine platform
immunogenicity
in vivo electroporation
Ebola
Lassa
Online Access:https://www.mdpi.com/1999-4915/13/3/382
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spelling doaj-06292c7bc4954bc78774733aa152463f2021-02-28T00:03:48ZengMDPI AGViruses1999-49152021-02-011338238210.3390/v13030382Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever VirusesJingjing Jiang0Stephanie J. Ramos1Preeti Bangalore2Dustin Elwood3Kathleen A. Cashman4Sagar B. Kudchodkar5Katherine Schultheis6Holly Pugh7Jewell Walters8Jared Tur9Jian Yan10Ami Patel11Kar Muthumani12Connie S. Schmaljohn13David B. Weiner14Laurent M. Humeau15Kate E. Broderick16Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAVaccine & Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAVaccine & Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAVaccine & Immunotherapy Center, The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAInovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USAThe emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and nonhuman primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases.https://www.mdpi.com/1999-4915/13/3/382DNA vaccineMultivalent vaccine platformimmunogenicityin vivo electroporationEbolaLassa
collection DOAJ
language English
format Article
sources DOAJ
author Jingjing Jiang
Stephanie J. Ramos
Preeti Bangalore
Dustin Elwood
Kathleen A. Cashman
Sagar B. Kudchodkar
Katherine Schultheis
Holly Pugh
Jewell Walters
Jared Tur
Jian Yan
Ami Patel
Kar Muthumani
Connie S. Schmaljohn
David B. Weiner
Laurent M. Humeau
Kate E. Broderick
spellingShingle Jingjing Jiang
Stephanie J. Ramos
Preeti Bangalore
Dustin Elwood
Kathleen A. Cashman
Sagar B. Kudchodkar
Katherine Schultheis
Holly Pugh
Jewell Walters
Jared Tur
Jian Yan
Ami Patel
Kar Muthumani
Connie S. Schmaljohn
David B. Weiner
Laurent M. Humeau
Kate E. Broderick
Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses
Viruses
DNA vaccine
Multivalent vaccine platform
immunogenicity
in vivo electroporation
Ebola
Lassa
author_facet Jingjing Jiang
Stephanie J. Ramos
Preeti Bangalore
Dustin Elwood
Kathleen A. Cashman
Sagar B. Kudchodkar
Katherine Schultheis
Holly Pugh
Jewell Walters
Jared Tur
Jian Yan
Ami Patel
Kar Muthumani
Connie S. Schmaljohn
David B. Weiner
Laurent M. Humeau
Kate E. Broderick
author_sort Jingjing Jiang
title Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses
title_short Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses
title_full Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses
title_fullStr Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses
title_full_unstemmed Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses
title_sort multivalent dna vaccines as a strategy to combat multiple concurrent epidemics: mosquito-borne and hemorrhagic fever viruses
publisher MDPI AG
series Viruses
issn 1999-4915
publishDate 2021-02-01
description The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and nonhuman primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases.
topic DNA vaccine
Multivalent vaccine platform
immunogenicity
in vivo electroporation
Ebola
Lassa
url https://www.mdpi.com/1999-4915/13/3/382
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