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Influenza Vaccines: The Good, The Bad, and The Eggs PowerPoint PPT Presentation

Influenza Vaccines: The Good, The Bad, and The Eggs Stacey Schultz-Cherry Assistant Professor Department of Medical Microbiology & Immunology Makes You feel Like … Primarily children Influenza Virus Viral shedding - 1 dpi Flu-like symptoms 1- 8 dpi Transient lymphocytopenia

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Influenza Vaccines: The Good, The Bad, and The Eggs

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Influenza Vaccines: The Good, The Bad, and The Eggs

Stacey Schultz-Cherry

Assistant Professor

Department of Medical Microbiology & Immunology


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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


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This year…


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“Ship of Flu”

Flu


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1918 Pandemic


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Cause of world-wide disease episodes

PANDEMICS

Subtype

1918Spanish fluH1N1

1933Influenza virus discovered

1957Asian fluH2N2

1968Hong Kong fluH3N2

1977 Russian (swine) fluH1N1

1997Avian flu???H5N1


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Avian Influenza


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


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Influenza viruses are unique among respiratory tract viruses undergo significant antigenic variation.

Antigenic drift vs. antigenic shift


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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


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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.


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Avian Influenza A (H5N1):A Persistent Threat


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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


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Avian Influenza A (H5N1):A Persistent Threat


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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


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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)


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  • 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.


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  • 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


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How is the Vaccine Produced

Decide on the Strains

  • WHO: Northern Hemisphere (Feb)

  • CDC: Prepare seed Virus

  • 9 months later have vaccine


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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.


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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


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WHO Surveillance Network

Situation continues to get more complicated..


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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


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Prophylactics & Antivirals

  • Vaccination

  • M2 Blockers

    * Amantadine

    * Rimantadine

  • NA inhibitors

    * Zanamavir

    * Oseltamavir


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Life Cycle of Influenza Virus


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Increasing resistance!!


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  • 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.


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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.


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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.


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