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Flu Immunizations: The Great, The Awful, and The Eggs

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  1. Influenza Vaccines: The Good, The Bad, and The Eggs Stacey Schultz-Cherry Assistant Professor Department of Medical Microbiology & Immunology

  2. Makes You feel Like … Primarily children Influenza Virus • Viral shedding - 1 dpi • Flu-like symptoms 1- 8 dpi • Transient lymphocytopenia • Immunosuppression • Increased cytokines • Inflammatory response • GI symptoms • Croup • Otitis media • Magically at d4 –viral clearance • Recovery and immunity!! • Doesn’t always work this way

  3. This year…

  4. “Ship of Flu” Flu

  5. 1918 Pandemic

  6. Cause of world-wide disease episodes PANDEMICS Subtype 1918 Spanish flu H1N1 1933 Influenza virus discovered 1957 Asian flu H2N2 1968 Hong Kong flu H3N2 1977 Russian (swine) flu H1N1 1997 Avian flu??? H5N1

  7. Avian Influenza

  8. www.osc.edu/.../si/projects/flu_virus/flu-3d.gif

  9. Influenza viruses are unique among respiratory tract viruses undergo significant antigenic variation. Antigenic drift vs. antigenic shift

  10. Highly Pathogenic Avian H5N1 Influenza Viruses in Humans Hong Kong, 1997 • First evidence of direct avian-to-human infection and serious disease in humans • 18 confirmed cases, 6 deaths • Hong Kong, 2003 • HK residents returning from southern China • 2 confirmed cases, one death • Since 2005 348 confirmed cases, 215 deaths Actual # of people infected - unknown

  11. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO Total number of cases includes number of deaths. WHO reports only laboratory-confirmed cases. All dates refer to onset of illness.

  12. Avian Influenza A (H5N1):A Persistent Threat

  13. Avian Influenza A (H5N1): Clinical Presentation Diarrhea Shortness of breath Severe Cases Leucopenia Lymphopenia Impaired liver function with elevated liver enzymes Prolonged clotting times and renal impairment. The lymphocyte count appears to be the most valuable parameter for identification of patients who are at risk of progression to severe illness http://influenzareport.com

  14. Avian Influenza A (H5N1):A Persistent Threat

  15. Influenza Vaccines Unique • First to offer population-wide protection against a changing virus (HIV??) • Production time and guesswork • No efficacy testing – double-blind testing • Safety testing for long-term side effects – non existent

  16. Seasonal Influenza Vaccines Types of Vaccine • “Flu Shot” – inactivated, trivalent • “FluMist” – attenuated live-virus What’s in the Vaccine? • H1N1, H3N2, Influenza B • Inactivated – Thimerosal (Mercury)

  17. People who should get vaccinated each year are: • People at high risk for complications: • Children aged 6 months – 5 yr • Pregnant women, • > 50 yr • Chronic medical conditions • Nursing homes and other long term care facilities • People who live with or care for those at high risk for complications from flu: • Household contacts of chronic or children < 6 mo • Healthcare workers • Use of the Nasal Spray Flu Vaccine • Healthy* people 2-49 years; Not pregnant.

  18. Who Should Not Be Vaccinated • Egg allergies • Severe reaction to previos influenza vaccination • Guillain-Barré syndrome (GBS) within 6 weeks of getting an influenza vaccine previously • < 6 months of age • Moderate or severe illness with a fever

  19. How is the Vaccine Produced Decide on the Strains • WHO: Northern Hemisphere (Feb) • CDC: Prepare seed Virus • 9 months later have vaccine

  20. Seasonal Vaccine Problems • Strain Choice – Eggs? • Production time and limitations • Efficacy — an A/Brisbane/59/2007 (H1N1)-like virus;— an A/Brisbane/10/2007 (H3N2)-like virus;*— a B/Florida/4/2006-like virus.# * A/Brisbane/10/2007 is a current southern hemisphere vaccine virus.# B/Florida/4/2006 and B/Brisbane/3/2007 (a B/Florida/4/2006-like virus) are current southern hemisphere vaccine viruses.

  21. Pandemic Vaccines? Problems • What Strain? • Production Time • Immunogenicity – subunits, VLPs, baculovirus, viral vectors, live virus, adjuvants • Who should get it? • When should it be administered • Eggs vs cell culture • Antigenic shift and drift • HIGH CONTAINMENT LABS

  22. WHO Surveillance Network Situation continues to get more complicated..

  23. Pandemic Vaccines? Problems • What Strain? • Production Time • Immunogenicity – subunits, VLPs, baculovirus, viral vectors, live virus, adjuvants • Who should get it? • When should it be administered • Eggs vs cell culture • Antigenic shift and drift • HIGH CONTAINMENT LABS

  24. Prophylactics & Antivirals • Vaccination • M2 Blockers * Amantadine * Rimantadine • NA inhibitors * Zanamavir * Oseltamavir

  25. Life Cycle of Influenza Virus

  26. Increasing resistance!!

  27. Ten things you need to know about pandemic influenza • 1. Pandemic influenza is different from avian influenza. • 2. Influenza pandemics are recurring events. • 3. The world may be on the brink of another pandemic. • 4. All countries will be affected. • global spread is inevitable • less than 3 months? • 5. Widespread illness will occur. • 6. Medical supplies will be inadequate. • 7. Large numbers of deaths will occur. • 8. Economic and social disruption will be great. • 9. Every country must be prepared. • 10. WHO will alert the world when the pandemic threat increases.

  28. Influenza vaccines are no magic bullet. Work on a pandemic vaccine continues in several countries, but the true efficacy of a vaccine would become apparent only when used. Supply is also an issue: clinical trials suggest that current vaccine production would be unable to provide enough doses for the global population in the event of a pandemic. Also, H5N1 vaccine strains show a lower production yield than usual seasonal vaccine strains, explained Dr Marie-Paule Kieny, director of WHO's Initiative for Vaccine Research: "Moreover, H5N1 split or subunit-inactivated vaccines seem to be less immunogenic than their seasonal counterparts. Therefore, research efforts should be invested into understanding the basis for these differences, and into development of strains which do not have these two disadvantages". Vaccine or no, the problem and solution are at the animal level. "If we can get a good handle on control in animals then the human threat disappears but there is still a long way to go towards achieving this, with many unanswered questions," said Peiris.

  29. THIS JUST IN...!!!!!!!!! In an attempt to thwart the spread of bird flu, President George W. Bush has bombed the Canary Islands. Turkey is next.