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Synthetic nucleic acid antibody prophylaxis confers rapid and durable protective immunity against Zika virus challenge
- Source :
- Human Vaccines & Immunotherapeutics
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
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–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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 2164554X and 21645515
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Human Vaccines & Immunotherapeutics
- Accession number :
- edsair.doi.dedup.....ee49c14e8e6becbdc77a8b66a18d0ac5