Synthetic nucleic acid antibody prophylaxis + DNA vaccine confers rapid and durable protective immunity against Zika virus
Hyeree Choi1, Sagar B. Kudchodkar1, Emma Reuschel1, Kanika Asija1, Piyush Borole1, Bryan Griffin2, Rianne Esquivel1, Ami Patel1, Stephanie Ramos3, Kimberly A. Kraynyak3, Charles Reed3, Kate E. Broderick3, Laurent Humeau3, Scott White3, J Joseph Kim3, Gary Kobinger4, David B. Weiner1, Kar Muthumani1 1Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, USA 2National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada 3Inovio Pharmaceuticals, Plymouth Meeting, PA, USA 4Université Laval, Quebec City, QC, Canada, Objectives: Significant concern has been raised over the past two years from the increased global spread of the mosquito-borne flavivirus, Zika (ZIKV). Accompanying this spread has been an increase in cases of the devastating birth defect microcephaly as well as cases of Guillain-Barre 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 protection and durable protection than traditional vaccination. Methods: A novel immune-based prophylaxis/therapy strategy entailing the facilitated delivery of a synthetic DNA consensus prME antigen vaccine along with designed DNA encoded biologically active anti-Zika envelope monoclonal antibodies (DMAb) was developed and evaluated for antiviral efficacy, as well as for the ability to overcome shortcomings inherent with conventional active vaccination or passive immunotherapy. This strategy utilizes Cellectra-EP® technology to deliver transient DNA transgene to skeletal muscle for in vivo production and secretion. Results:A collection ofDMAbs were developed which were potent against ZIKA in vitro and could be expressed in serum with in 24-48 hours of administration in vivo. The DNA vaccine was also potent after adaptive immunity was developed, protecting against infection, brain and testes pathology in relevant mouse challenge models and in NHP challenge. Delivery of potent DMAbs protected mice from viral challenge within days of delivery. Combined injection of DMAb and DNA vaccine afforded rapid and long-lived protection in these same challenge models, providing an important demonstration of the advantage of this synergistic approach to pandemic outbreaks. Conclusion: We show that simple DNA formulations by enhanced delivery provide improved protection in relevant ZIKA challenges. This novel approach has advantages in emerging infectious diseases and pandemic vaccine strategies including Zika.
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