Lecture 11 - Future Vaccines

Lecture 11 - Future Vaccines - FUTURE VACCINES Replicons,...

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EVO FUTURE VACCINES Replicons, Ghosts and Vaccines Against Shigella Edwin Oaks, Ph.D. George Mason University BIOL 420 Section 2
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EVO Replicons Ghost Vaccines Shigella Vaccines Topics
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EVO Virus Replication Cycle There are several phases of viral replication: 1. Attachment 2. Penetration 3. Uncoating 4. Synthesis phase 5. Maturation 6. Release
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EVO Synthesis Phase This phase includes three overlapping steps: 1. Synthesis of virus-specific mRNA - all viruses must do this 1. Synthesis of viral genes - various replication strategies Pathways for synthesis of viral nucleic acids vary considerably among the different viral families. 1. Translation of viral mRNA into polypeptides The translation of mRNA into polypeptides depends on the host’s protein synthesis apparatus and is the same for all viruses Some viral polypeptides are cleaved by proteases at specific sites into two or more functional units
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EVO Maturation Maturation is the formation of infectious viral particles (virions) As soon as the capsid proteins reach a threshold concentration, self-assembly results in the formation of capsids This process is facilitated by the presence of nucleic acids of the appropriate size Most of the capsids contain viral genomes (nucleocapsids) Some are empty and contain host genes (pseudovirions)
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EVO Overview of Viral Replication Uncoating Penetration Attachment Transcription Transport to nucleus Nucleus mRNA Translation Capsid Assembly Release Budding Cytoplasm
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EVO Overview of Viral Replication Uncoating Penetration Attachment Transcription Transport to nucleus Nucleus mRNA Translation Capsid Assembly Release Budding Cytoplasm In DENDRITIC Cell (an APC)
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EVO REPLICONS What are Replicons Derived from RNA viruses Consist of virion and RNA genome Infectious Delivers RNA into cell Get expression of antigen gene » But no viral progeny Replicons synthesize large quantities of protein antigen in infected cells Effective presentation to immune system
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EVO Replicon Vaccines RNA Virus Replicons Two types of RNA viruses “+” stranded » Genome is equivalent to mRNA » First step after infection is translation of replicase gene from parental RNA genome » Is infectious Genomes can be produced in the lab » cDNA (- sense), copied with RNA polymerase to yield +RNA “-” stranded Genome needs to be transcribed to “+” strand » Genome is complimentary to mRNA » Can use “+” transcripts to infect cells
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EVO Examples of RNA viruses Positive-stranded RNA viruses Alphaviruses Sindbis virus (SIN)
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Lecture 11 - Future Vaccines - FUTURE VACCINES Replicons,...

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