A novel synthetic DNA vaccine elicits protective immune responses against Powassan virus.

Autor: Choi H; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Kudchodkar SB; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Ho M; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Reuschel EL; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Reynolds E; Department of Microbiology and Immunology, SUNY Center for Environmental Health and Medicine, SUNY Upstate Medical University, Syracuse, New York, United States of America., Xu Z; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Bordoloi D; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Ugen KE; Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida, United States of America., Tebas P; Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Kim J; R&D, Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, United States of America., Abdel-Mohsen M; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Thangamani S; Department of Microbiology and Immunology, SUNY Center for Environmental Health and Medicine, SUNY Upstate Medical University, Syracuse, New York, United States of America., Weiner DB; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Muthumani K; Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2020 Oct 29; Vol. 14 (10), pp. e0008788. Date of Electronic Publication: 2020 Oct 29 (Print Publication: 2020).
DOI: 10.1371/journal.pntd.0008788
Abstrakt: Powassan virus (POWV) infection is a tick-borne emerging infectious disease in the United States and North America. Like Zika virus, POWV is a member of the family Flaviviridae. POWV causes severe neurological sequalae, meningitis, encephalitis, and can cause death. Although the risk of human POWV infection is low, its incidence in the U.S. in the past 16 years has increased over 300%, urging immediate attention. Despite the disease severity and its growing potential for threatening larger populations, currently there are no licensed vaccines which provide protection against POWV. We developed a novel synthetic DNA vaccine termed POWV-SEV by focusing on the conserved portions of POWV pre-membrane and envelope (prMEnv) genes. A single immunization of POWV-SEV elicited broad T and B cell immunity in mice with minimal cross-reactivity against other flaviviruses. Antibody epitope mapping demonstrated a similarity between POWV-SEV-induced immune responses and those elicited naturally in POWV-infected patients. Finally, POWV-SEV induced immunity provided protection against POWV disease in lethal challenge experiments.
Competing Interests: KM and DBW note funding by Inovio Pharmaceuticals, PA, USA. KM discloses grant funding, industry collaborations, speaking honoraria, and fees for consulting. He has a patent application for DNA vaccine development and delivery of DNA encoded monoclonal antibodies. DBW notes that he and his laboratory have several commercial relationships with companies in the area of vaccines. These include him receiving consulting fees or stock ownership for Advisory/Review Board service, speaking support, or research support from commercial entities including a sponsored research agreement (SRA) from, has an ownership interest in, has patents filed with, and has received consulting and received speakers honoraria from Inovio; has received an SRA and consulting and speakers honoraria from GeneOne and Geneos; and has served on advisory boards for AstraZeneca and Sanofi. JJK is an employee at Inovio Pharmaceuticals. The other authors declare no competing financial interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Databáze: MEDLINE
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