Engineered alphavirus replicon vaccines based on known attenuated viral mutants show limited effects on immunogenicity
| Autor: | Christine A. Shaw, Gillis R. Otten, Giulietta Maruggi, Peter W. Mason, Clayton W. Beard |
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| Jazyk: | angličtina |
| Předmět: |
Sindbis virus
Alphavirus replicon vaccine viruses Genetic Vectors Alphavirus Biology Vaccines Attenuated Virus Encephalitis Virus Venezuelan Equine Interferon-gamma Mice 5′ UTR Antigen Interferon Virology Secondary structure Attenuating mutation medicine Animals Replicon Antigens Antigen expression Drug Carriers Mice Inbred BALB C Vaccines Synthetic Innate immune system Immunogenicity Gene Expression Profiling Viral Vaccines biochemical phenomena metabolism and nutrition biology.organism_classification Sindbis Virus 5' Untranslated Regions Interferon induction medicine.drug |
| Zdroj: | Virology. (1-2):254-264 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2013.07.021 |
| Popis: | The immunogenicity of alphavirus replicon vaccines is determined by many factors including the level of antigen expression and induction of innate immune responses. Characterized attenuated alphavirus mutants contain changes to the genomic 5′ UTR and mutations that result in altered non-structural protein cleavage timing leading to altered levels of antigen expression and interferon (IFN) induction. In an attempt to create more potent replicon vaccines, we engineered a panel of Venezuelan equine encephalitis-Sindbis virus chimeric replicons that contained these attenuating mutations. Modified replicons were ranked for antigen expression and IFN induction levels in cell culture and then evaluated in mice. The results of these studies showed that differences in antigen production and IFN induction in vitro did not correlate with large changes in immunogenicity in vivo. These findings indicate that the complex interactions between innate immune response and the replicon′s ability to express antigen complicate rational design of more potent alphavirus replicons. |
| Databáze: | OpenAIRE |
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