Single-round infectious particles enhance immunogenicity of a DNA vaccine against West Nile virus
| Autor: | Wen J Liu, Christopher C. Pollitt, David C. Clark, Roy A. Hall, David C. Chang, Andreas Suhrbier, Alexander A. Khromykh, Itaru Anraku |
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| Rok vydání: | 2008 |
| Předmět: |
viruses
Genetic Vectors Biomedical Engineering Bioengineering Transfection Applied Microbiology and Biotechnology Virus Flavivirus Infections DNA vaccination Mice Drug Delivery Systems Virus-like particle Kunjin virus Vaccines DNA Animals Neutralizing antibody biology Virion RNA Genetic Therapy biochemical phenomena metabolism and nutrition biology.organism_classification Virology Flavivirus Treatment Outcome Capsid Drug Design biology.protein Molecular Medicine Biotechnology |
| Zdroj: | Nature Biotechnology. 26:571-577 |
| ISSN: | 1546-1696 1087-0156 |
| DOI: | 10.1038/nbt1400 |
| Popis: | DNA vaccines encoding replication-defective viruses are safer than inactivated or live attenuated viruses but may fail to stimulate an immune response sufficient for effective vaccination. We augment the protective capacity of a capsid-deleted flavivirus DNA vaccine by co-expressing the capsid protein from a separate promoter. In transfected cells, the capsid-deleted RNA transcript is replicated and translated to produce secreted virus-like particles lacking the nucleocapsid. This RNA is also packaged with the help of co-expressed capsid protein to form secreted single-round infectious particles (SRIPs) that deliver the RNA into neighboring cells. In SRIP-infected cells, the RNA is replicated again and produces additional virus-like particles, but in the absence of capsid RNA no SRIPs are formed and no further spread occurs. Compared with an otherwise identical construct that does not encode capsid, our vaccine offers better protection to mice after lethal West Nile virus infection. It also elicits virus-neutralizing antibodies in horses. This approach may enable vaccination against pathogenic flaviviruses other than West Nile virus. |
| Databáze: | OpenAIRE |
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