@article{b462dc14ea734517a8034e4e4bcb0367,
title = "Synthetic nucleic acid antibody prophylaxis confers rapid and durable protective immunity against Zika virus challenge",
abstract = "Significant concerns have arisen over the past 3 y from the increased global spread of the mosquito-borne flavivirus, Zika. Accompanying this spread has been an increase in cases of the devastating birth defect microcephaly as well as of Guillain–Barr{\'e} syndrome in adults in many affected countries. Currently there is no vaccine or therapy for this infection; however, we sought to develop a combination approach that provides more rapid and durable protection than traditional vaccination alone. A novel immune-based prophylaxis/therapy strategy entailing the facilitated delivery of a synthetic DNA consensus prME vaccine along with DNA-encoded anti-ZIKV envelope monoclonal antibodies (dMAb) were developed and evaluated for antiviral efficacy. This immediate and persistent protection strategy confers the ability to overcome shortcomings inherent with conventional active vaccination or passive immunotherapy. A collection of novel dMAbs were developed which were potent against ZIKV and could be expressed in serum within 24–48 h of in vivo administration. The DNA vaccine, from a previous development, was potent after adaptive immunity was developed, protecting against infection, brain and testes pathology in relevant mouse challenge models and in an NHP challenge. Delivery of potent dMAbs protected mice from the same murine viral challenge within days of delivery. Combined injection of dMAb and the DNA vaccine afforded rapid and long-lived protection in this challenge model, providing an important demonstration of the advantage of this synergistic approach to pandemic outbreaks.",
keywords = "DNA vaccine, Zika virus, antibodies, dMAb-DNA encoded monoclonal antibodies, immunotherapy, vaccination",
author = "Hyeree Choi and Kudchodkar, {Sagar B.} and Reuschel, {Emma L.} and Kanika Asija and Piyush Borole and Sangya Agarwal and {Van Gorder}, Lucas and Reed, {Charles C.} and Gayathri Gulendran and Stephanie Ramos and Broderick, {Kate E.} and Kim, {J. Joseph} and Ugen, {Kenneth E.} and Gary Kobinger and Siegel, {Don L.} and Weiner, {David B.} and Kar Muthumani",
note = "Funding Information: The studies described in this manuscript were funded by a grant from the Wistar Science Discovery Award to KM. We would like to thank the Wistar Flow Cytometry Facility and Animal Facility for their technical assistance. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Funding Information: This work was supported by the Wistar Science Discovery fund awarded to K.M. The studies described in this manuscript were funded by a grant from the Wistar Science Discovery Award to KM. We would like to thank the Wistar Flow Cytometry Facility and Animal Facility for their technical assistance. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Funding Information: CCR, SR, KEB, LMH, and JJK are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options. KM discloses grant funding, industry collaborations, speaking honoraria, and fees for consulting. He has received consulting fees from Inovio Pharmaceuticals related to DNA and dMAb vaccine development. He has a patent application for DNA vaccine development and delivery of DNA-encoded monoclonal antibodies pending to Inovio Pharmaceuticals. Remuneration includes direct payments. DBW discloses grant funding, SAB and Board service, industry collaborations, speaking honoraria, and fees for consulting. His service includes serving on scientific review committees and advisory boards. Remuneration includes direct payments and/or stock or stock options. He notes potential conflicts associated with this work with Pfizer, Bristol Myers Squibb, Inovio Pharmaceuticals, Merck, VGXI, Geneos, AstraZeneca, and potentially others. Licensing of technology from this laboratory has created over 150 jobs in the biotech/pharma industry. The other authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2019, {\textcopyright} 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2020",
month = apr,
day = "2",
doi = "10.1080/21645515.2019.1688038",
language = "English (US)",
volume = "16",
pages = "907--918",
journal = "Human Vaccines and Immunotherapeutics",
issn = "2164-5515",
publisher = "Landes Bioscience",
number = "4",
}