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vaccine - Vaccines Successes of the Past Possibilities for...

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1 Vaccines Successes of the Past Possibilities for the Future
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2 Vaccines Immunity to viral infections usually depends on the development of an immune response to Antigens on the virus surface Antigens on the virus-infected cell In most cases response to internal proteins has little effect on humoral immunity to infection Humoral antibodies can be important diagnostically (HIV)
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3 Vaccines Minor role for internal proteins can be seen in influenza pandemics New flu viral strain contains a novel glycoprotein Pandemic virus contains internal proteins to which the population has already been exposed Nevertheless the CTL response to internal proteins is important Surface glycoprotein = protective immunogen which must be identified for a logical vaccine
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4 Vaccines Some viruses have more than one surface protein Influenza (Orthomyxovirus) Hemagglutinin - attaches virus to cell receptor Neuraminidase - involved in release of virus from cell Hemagglutinin is major target: stimulates neutralizing antibody
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5 Vaccines Neutralization may result from: Binding of antibody to site on virus surface - block interaction with receptor Aggregation of virus by polyvalent antibody Complement-mediated lysis
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6 Vaccines Addition points to note: Site in body at which virus replicates Three major sites for viral replication
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7 Three major sites for viral replication Mucosal surfaces of respiratory tract and GI tract. Rhino; myxo; corona; parainfluenza; respiratory syncytial; rota Infection at mucosal surfaces followed by spread systemically via blood and/or neurones to target organs: picorna; measles; mumps; HSV; varicella; hepatitis A and B Direct infection of blood stream via needle or bites and then spread to target organs: hepatitis B; alpha; flavi; bunya; rhabdo Local immunity via IgA very important in 1 and 2.
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8 There is little point in having a good neutralizing humoral antibody in the circulation when the virus replicates, for example, in the upper respiratory tract. Clearly, here secreted antibodies are important. Although in the case of influenza serum antibodies may be important
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9 Vaccines - Problems Different viruses may cause similar disease --e.g. common cold Antigenic drift and shift -- especially true of RNA viruses and those with segmented genomes Shift: reassortment of segmented genomes (‘flu A but not rota or ‘flu B) Drift: rapid mutation - retroviruses Large animal reservoirs - Reinfection may occur
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10 Vaccines - Problems Integration of viral DNA . Vaccines will not work on latent virions unless they express antigens on cell surface. In addition, if vaccine virus integrates it may cause problems Transmission from cell to cell via syncytia Recombination of the virulent strain or of the vaccine virus
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11 Smallpox Mummies China/India Crusaders W Europe: fatality rate 25% History changed: Cortes Louis XIV
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12 Smallpox Variolation 1% v. 25% mortality Life-long immunity: No drift or shift (proof reading) UK: 1700’s China 1950 Pakistan/Afghanistan/Ethiopia 1970
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