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Canada (492,453)
Pathology (104)
PATH 3610 (104)
Rob Foster (26)
Lecture 5

Lecture 5 notes

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University of Guelph
PATH 3610
Rob Foster

LECTURE 5 – VACCINES/ANTIVIRALS Requirements of an effective vaccine and contrary measures to effective vaccine design • Safety – must not cause disease • Minimal side effects • Induction of protective immune response (efficacious) • Practical o Cost/dose must not be prohibitive o Vaccine should be biologically stable o Vaccine should be easy to administer o The public must see more benefit than risk Pros and cons of live virus and inactivated vaccines Conditions favoring virus eradication Contrary factor to the design of an effective vaccine - Antigenic variation with many serotypes - Animal or environmental reservoirs - Failure to form antibody - Antibody may enhance infection - Infection of essential cells of the immune system - Integration of viral genome into host genome Immunization Strategies 1. Non-living virus vaccines a. Inactivated whole virus vaccines i. Inactivation of viruses: formalin, β-propiolactone; adjuvants b. Virus like particles (VLPs) – are comprised of multiple copies of a protein antigen that, when assembled together, mimic the conformation of a native virus c. Subunit vaccines 2. Live-virus vaccines 3. Other a. Anti-idiotypic antibody – they bear internal images of neutralization epitopes of viruses; functions like an antigen -> protective Abs induced. i. Idiotype – site where an antigen binds to an antibody b. DNA vaccines – DNA coding for foreign antigen is directly injected into the animal and the foreign antigen is produced by the host cells i. DNA acts as a PAMP and stimulates TLR c. Edible vaccines – transgenic plants expressing a protective antigen; plants that can be consumed raw. Subunit vaccines It is a type of non-living virus vaccine. - Viral protein purified from virions o E.g. influenza virus – HA, NA o Hepatitis B surface antigen - Recombinant proteins o Expression of recombinant proteins is economically feasible o Purification from cellular materials o Native conformation o Expression systems – prokaryotic cells, yeast, insect cells, mammalian cells, VLPs - Synthetic peptides o a string of amino acids chemically synthesized o T-cell epitopes are naturally presented in the form of a peptide o Safe and stable o Poorly immunogenic – requires conjugates and adjuvants o Too specific and natural variants can easily escape Live virus vaccines Attenuated (in virulence) virus vaccines - e.g. vaccine for polio - deletion mutants Methods of attenuation - serial passage in cell cultures - serial passage in animals other than original host - serial passage in embryonated eggs - passage in the presence of mutagens - passage at non-permissive temperature - molecular methods: o site-directed mutagenesis o deletions o transcriptional modif
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