Synthetic nucleic acid antibody prophylaxis confers rapid and durable protective immunity against Zika virus challenge
| Autor: | Gayathri Gulendran, David B. Weiner, Charles C. Reed, Sagar B. Kudchodkar, Kanika Asija, Hyeree Choi, Karuppiah Muthumani, Lucas Van Gorder, Sangya Agarwal, Piyush Borole, Don L. Siegel, Emma L. Reuschel, J. Joseph Kim, Stephanie Ramos, Kenneth E. Ugen, Gary P. Kobinger, Kate E. Broderick |
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| Rok vydání: | 2019 |
| Předmět: |
dMAb-DNA encoded monoclonal antibodies
DNA vaccine Protective immunity viruses medicine.medical_treatment 030231 tropical medicine Immunology Antibodies Viral DNA vaccination Zika virus Mice 03 medical and health sciences 0302 clinical medicine Nucleic Acids medicine Animals antibodies Immunology and Allergy 030212 general & internal medicine Pharmacology Synthetic nucleic acid biology Zika Virus Infection business.industry Viral Vaccines Zika Virus Immunotherapy vaccination biology.organism_classification Antibodies Neutralizing Virology Vaccination Flavivirus biology.protein immunotherapy Antibody business Research Paper |
| Zdroj: | Human Vaccines & Immunotherapeutics |
| ISSN: | 2164-554X 2164-5515 |
| DOI: | 10.1080/21645515.2019.1688038 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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