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Influenza Vaccines

Influenza Vaccines. MedCh 401 Lecture 5. Occurrence of Influenza in U.S. ~48 million cases per year ~3.9 million hospitalized 20,000 deaths >40,000 deaths in bad epidemic year >90% in persons >65 years of age Seasonal disease - winter in N. Hemisphere. Influenza virus.

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Influenza Vaccines

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  1. Influenza Vaccines MedCh 401 Lecture 5 KL Vadheim Lecture 4

  2. Occurrence of Influenza in U.S. • ~48 million cases per year • ~3.9 million hospitalized • 20,000 deaths • >40,000 deaths in bad epidemic year • >90% in persons >65 years of age • Seasonal disease - winter in N. Hemisphere KL Vadheim Lecture 4

  3. Influenza virus • Orthomyxovirus • Single-stranded RNA genome • lacks proof-reading ability of DNA genomes • Segmented genome • increases potential for genetic reassortment • Continuous evolution of genome and antigens KL Vadheim Lecture 4

  4. Influenza virus • Highly infectious • Affects all age groups • Most common cause of lower respiratory tract infections • Three antigen types KL Vadheim Lecture 4

  5. Influenza Antigen types • Type A • infection occurs most frequently • accounts for majority of morbidity and mortality • moderate to severe illness • perpetuated in nature by wildfowl • usually not pathogenic to natural host • normally don’t change or evolve KL Vadheim Lecture 4

  6. Influenza Antigen Types II • Type B • responsible for regional epidemics • less severe disease than A • affects primarily children • affects humans only • Type C • rarely causes epidemics • associated with sporadic human cases KL Vadheim Lecture 4

  7. Influenza A subtypes • Determined by surface antigens: • Hemagglutinin - virus attachment to cells • H1 • H2 • H3 • Neuraminidase - virus penetration into cells • N1 • N2 KL Vadheim Lecture 4

  8. Reassortant viruses • Natural and induced process • Process is used to increase replication of new viruses (e.g., vaccine strains) to high titers • Produced by: • simultaneous infection of check embryo with antigenically dissimilar parental viruses • select by passage of post-reassortment virus with antibody suppressing antigens of high-yield donor KL Vadheim Lecture 4

  9. Antigenic drift • Minor change in surface antigens • Antigenic mutants of surface antigens H and N emerge by cumulative point mutations • Are selected by antibody to previous predominant virus • Continuous process • Occurs in types A, B, C KL Vadheim Lecture 4

  10. Antigenic Shift • Due to recombination between Type A viruses • Major changes (H, N) from currently circulating virus • Spread rapidly due to lack of protection in population • Often causes pandemic • May or may not cause more severe disease KL Vadheim Lecture 4

  11. Influenza Prevalence • 1918-1919 - H1N1 • severe • highly infectious • ~20 million deaths worldwide • 1957 - H2N2 • mild • 1-4 million deaths worldwide • 1968- H3N2 • Moderate • Current strains - H3N2 and H1N1 KL Vadheim Lecture 4

  12. Definitions • Epidemic • Outbreak of an infectious disease that spreads rapidly • Occurrence of an infectious disease at a higher rate than normal • Increase in morbidity over normal incidence • Severity of disease may or may not increase • Mortality may or may not increase (but often does with flu epidemics) KL Vadheim Lecture 4

  13. Definitions • Pandemic • Epidemic over a wide geographic area and affecting a large proportion of the population • Morbidity increases over larger population area • Mortality may or may not rise KL Vadheim Lecture 4

  14. Flu vaccines • Trivalent • Manufactured each year for specific viruses • Expire in June of each year KL Vadheim Lecture 4

  15. Flu Vaccines KL Vadheim Lecture 4

  16. Types of Manufacturing Processes • Chicken embryo process • takes 10 weeks • campaign-based • high yield (millions of doses) • Cell culture • continuous process • lower yield (< 1 million doses) KL Vadheim Lecture 4

  17. Whole virus Flu Manufacturing I • Grow and purify each virus individually • Harvest culture fluid • sP: inactivate with formaldehyde • Concentrate with centrifugation • Purify with sucrose gradients • GSK, sP: solubilize virus with detergent • Novartis: inactivate with b-propriolactone KL Vadheim Lecture 4

  18. Whole virus Flu Manufacturing II • Further purification • GSK: inactivation with sodium deoxycholate and formaldehyde • All three purified, inactivated strains are formulated into split virus solutions KL Vadheim Lecture 4

  19. Live Flu vaccine production • Grow genetically attenuated viral strains in cell culture • Purify • Formulate KL Vadheim Lecture 4

  20. Flu Vaccines KL Vadheim Lecture 4

  21. Flu Symptoms • Incubation period 1-4 days • Abrupt onset of fever, myalgia, sore throat, dry cough, headache • ~50% of people develop these classical symptoms • Viremia rare • Viral shedding in respiratory secretions for 5-10 days KL Vadheim Lecture 4

  22. Transmission • Person-to-person • Respiratory droplets • Animal to human rare KL Vadheim Lecture 4

  23. Flu • Deaths commonly due to pneumonia from secondary infections: • S. pneumonia • H. influenzae • S. aureus KL Vadheim Lecture 4

  24. Flu Pandemics • Less seasonally restricted than normal flu • Are random events • May or may not demonstrate increased mortality KL Vadheim Lecture 4

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