[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
Hum Vaccin Immunother. 2019 Dec 4:1-12. doi: 10.1080/21645515.2019.1688038. [Epub ahead of print]
Synthetic nucleic acid antibody prophylaxis confers rapid and durable protective immunity against Zika virus challenge.
Choi H1, Kudchodkar SB1, Reuschel EL1, Asija K1, Borole P1, Agarwal S1, Van Gorder L1, Reed CC2, Gulendran G3, Ramos S2, Broderick KE2, Kim JJ2, Ugen KE4, Kobinger G5, Siegel DL3, Weiner DB1, Muthumani K1.
Author information: 1 Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA. 2 R&D, Inovio Pharmaceuticals, Plymouth Meeting, PA, USA. 3 Department of Pathology & Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, PA, USA. 4 Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, USA. 5 Université Laval, Quebec City, QC, Canada.
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-Barré 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
PMID: 31799896 DOI: 10.1080/21645515.2019.1688038
Keywords: Zika Virus; Vaccines; Monoclonal antibodies; Immunotherapy; Animal models.