vaccine advisory committee flu vaccine - doh.wa.gov · at this time there is insufficient data to...
TRANSCRIPT
WA State DOH | 2
Influenza Overview:
4 main influenza virus types/strains:
• A/H3N2, A/H1N1, B/Yamagata, and B/Victoria
A/H3N2:
• Is the most virulent of the 4 strains
• Accounts for the majority of influenza-associated hospitalizations and influenza-associated deaths in the United States
• Accounts for the greatest disease burden among the older adult population
• Most common strain for 2017-18 season
• Vaccine effectiveness (VE) against H3N2 viruses has been around 30%
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Vaccine Effectiveness (VE) and Antigenic Drift
• VE• Lower VE against H3N2 viruses may be caused by egg-adapted
changes introduced when H3N2 viruses are optimized for growth in eggs.
• Antigenic Drift• Two types of genetic changes can impact the similarity between a
vaccine virus and circulating seasonal viruses (“antigenic drift”).• Genetic changes can occur when influenza viruses are grown in
eggs• Influenza viruses constantly undergo small genetic changes that
may result in antigenic changes. • Egg-adapted changes in H3N2 viruses are more complex and likely
to have antigenic implications that can make these H3N2 viruses less similar to circulating H3N2 viruses.
WA State DOH | 4
Antigenic Drift and the 2017-2018 Season
No significant antigenic drift has occurred among circulating wild-type influenza viruses at this time.
• Most (98%) of circulating H3N2 influenza viruses remain similar to the cell-grown reference viruses used in production
• However, a smaller percentage (70%) of circulating H3N2 viruses are similar to the egg-grown reference virus used in production
These differences are likely a result of egg-adapted changes introduced when the H3N2 virus was grown in eggs.
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Flu Vaccine Production Technologies
There are 3 production technologies used to develop flu vaccine:
• Egg-Based
• Cell-Based
• Recombinant
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Egg-Based Production
• Most common way that flu vaccines are made
• All 2017-18 presentations are egg-based
Step 1: Candidate vaccine viruses (CVVs) grown in eggs
Step 2: CVVs are then injected into fertilized hen’s eggs and incubated for several days to allow the viruses to replicate
Step 3: The virus-containing fluid is harvested from the eggs
Step 4: Influenza viruses for the vaccine are then inactivated (killed), and virus antigen is purified
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Egg-Based Influenza Vaccine Challenges
• Egg-adapted changes may result in antigenic shift with A/H3N2
• This production method requires large numbers of chicken eggs to produce vaccine and usually takes longer than other methods used to produce vaccine.
• Acquisition of eggs requires significant lead time
• Reliability and quality of embryonated egg supply can be compromised by avian influenza outbreaks
• Not all strains can grow well in eggs creating vaccine production challenges
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Recombinant Production
Step 1: HA protein is isolated from a naturally occurring (“wild type”) recommended vaccine viruses
Step 2: Proteins are combined with portions of another virus that grows well in insect cells
Step 3: This “recombinant” vaccine virus is then mixed with insect cells and allowed to replicate
Step 4: The flu HA protein is then harvested from these cells and purified
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Recombinant Benefits
• H3N2 components are genetically more similar to circulating H3N2 viruses than the egg-adapted viruses used for egg-based manufacturing
• Requires the shortest amount of production time
• Only 100% egg-free flu vaccine on the market
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Cell-Based Production
Step 1: Candidate vaccine viruses (CVVs) are identified
Step 2: CVVs are then inoculated into cultured Mamalian cells and allowed to replicate for a few days
Step 3: The virus-containing fluid is collected from the cells
Step 4: The virus antigen is purified
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Cell-Based Benefits
• Cell-based flu vaccine has the potential to offer better protection than traditional, egg-based flu vaccines as a result of being more similar to flu viruses in circulation
• Faster production than egg-based method
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Non Egg-Based Vaccine Options
Recombinant influenza vaccine (Flublok)
Cell-grown influenza vaccine (Flucelvax).
Trivalent/Quadrivalent Quadrivalent
Flublok is indicated for persons 18+ Flucelvax is indicted for persons 4+
Influenza Vaccines: https://www.cdc.gov/flu/protect/vaccine/vaccines.htm
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Ending Statements
At this time there is insufficient data to conclude that cell-based or recombinant vaccine are more effective than egg-based vaccine.
Additional data is needed (including vaccine effectiveness data) before policy decisions on this topic could be considered.
Per CDC:
While the use of cell-grown reference viruses and cell-based technology may offer the potential for better protection over traditional, egg-based flu vaccines because they result in vaccine viruses that are more similar to flu viruses in circulation, there are no data yet to support this. There is no preferential recommendation for one injectable flu vaccine over another.
https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm
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Discussion Questions
Does the science available at this time, compel VAC to recommend adding Flucelvax as a presentation for the 2018-2019 flu season?
Production of US Inactivated Influenza Vaccines Has Relied on Embryonated Chicken Eggs
~6 monthsWHO and US FDA decide vaccine formulation
Vaccine delivery
Split with ether and a detergent or solubilized using a detergent
Vaccine is purified by ultracentrifugation
Inactivated by formalin or β-propiolactone
Seed strains harvested in allantoic cavity ofembryonated eggs
Seed strains adapted for large-scale production
Seed strains sent to manufacturers
Candidate strains reassorted with master strain growing well in egg
WHO selects candidate strains from clinical isolates;FDA approvesor modifies selection
Monovalent bulk antigens are blended1
Concentration and purity of antigens are verified
Processing of vaccine
Propagation of vaccine strain
Seed strainevaluation
Strain selection and reassortantdevelopment Formulation
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FDA=Food and Drug Administration; WHO=World Health Organization.Gerdil C. Vaccine. 2003;21(16):1776-1779.
Subunit quadrivalent seasonal influenza vaccine contains 15 µg of HA per strain1
Vaccine production can begin at any time of the year, independent of egg availability, and can be scaled up rapidly relative to egg-based production
Surface antigen subunits extracted and purified
Harvested viruses Inactivated usingβ-propiolactone
Seed strainsreplicated in in MDCK cells
MDCK cellsuspensionsexpanded million-fold
Seed strains adapted for large-scale production
Seed strains sent to manufacturers
Candidate strains reassorted with master strain growing well in egg
WHO selects candidate strains from clinical isolates;FDA approvesor modifies selection
Monovalent bulk antigens are blended2
Concentration and purity of antigens are verified
Antigen purification
Virus propagation
Seed strainevaluation
Strain selection and reassortantdevelopment Formulation
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FDA=Food and Drug Administration; HA=hemagglutinin; MDCK cells=Madin-Darby canine kidney cells; WHO=World Health Organization.1. Food and Drug Administration (FDA). Clinical Review Flucelvax Quadrivalent. 2016;1-82. http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM504789.pdf. Accessed April 8, 2017. 2. Gregersen JP. Vaccine. 2008;26:3332-3340. 3. Mabrouk T et al. Dev Biol (Basel). 2002;110:125-134.
Cell- Based Production Process