title: Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Seleeke
authors.initials: S
authors.lastname: Flingai
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Plummer
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ami
authors.initials: A
authors.lastname: Patel
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
authors.affiliation: Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
authors.forename: Janess M
authors.initials: JM
authors.lastname: Mendoza
authors.affiliation: Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick
authors.affiliation: Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kar
authors.initials: K
authors.lastname: Muthumani
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D003429:Cross Reactions / Q000276:immunology; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D020014:K562 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests / Q000379:methods; D009696:Nucleic Acids / Q000276:immunology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D009696:Nucleic Acids; D014759:Viral Envelope Proteins