seminar 302 2014
TRANSCRIPT
Influenza A virus – From biology to vaccines
• Samita AndreanskyDepartments of Microbiology and
Immunology, Pediatrics and Medicine
Influenza kills 20-30,000 Americans each year. About 40,00 die in road accidents
Young and Elderly are most vulnerable
1918 Spanish Flu Approx 20-40 million deaths
America’s deaths from influenza were greater than the number of U.S. servicemen killed in any war
Series10
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Civil WWI 1918-19 WWII Korean Vietnam War Influenza War War
Thousands
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• The influenza virus is a upper respiratory tract infection caused by one of the influenza virus pathogens (Type A, B, or C).
• Although it is called a respiratory disease, it affects the whole body, making you feel sick all over.
http://www.nlm.nih.gov/medlineplus/ency/imagepages/17237.htm
Where does Influenza virus acts on the body
Virus – Host Interaction
Virus Attachment Protein: Hemagglutinin
Host receptor : Sialic Acid
viralzone.expasy.org
Host receptor specificity
• Tiny droplets that come from a person’s mouth and nose when they cough and sneeze.
• • Touching objects
contaminated with particles from an infected person’s nose and throat.
http://www.lungusa.org/diseases/c&f02/influenza.html#what
Transmission from person to person by:
• Symptoms begin 1-4 days after infection. • You can spread the flu before your symptoms start and
3-4 days after your symptoms appear. • The following symptoms of the flu can vary depending
on the type of virus, a person’s age and overall health:– Sudden onset of chills and fever (101 – 103 degrees F)– Sore throat, dry cough – Fatigue, malaise – Terrible muscle aches, headaches– Diarrhea– Dizziness
Symptoms
• A bacterial “superinfection” can develop when the influenza virus infects the lungs.
• The result? – The bacteria that live in the nose and throat can descend to the lungs
and cause bacterial pneumonia. • Who is most at risk?
– People over 50, infants, those with suppressed immune function or chronic diseases.
• Other complications include bronchitis, sinusitis and ear infections.
http://www.ecureme.com/atlas/version2001/atlas.asp
Complications of Flu
Influenza A virus
• Nucleic acid : RNA
• Enveloped virus
• Viral family: Orthomyxoviridae
• Three types• A, B, C
Influenza viruses are small.Average eukaryotic cells is 10,000 nm in diameter (10 microns) 100 times bigger than the influenza virus diameter
Different Species – Different Genes
A/Fujian/411/2002 (H3N2)
NeuraminidaseHemagglutini
n
Type of nuclearmaterial
Virustype
Geographicorigin
Strainnumber
Year of isolation
HA and NA
substrain
Virus Nomenclature
Serotypes in humans
HA 1-16NA 1-9
Drift and Shift generates new viruses
Evolutionary Survival Strategy for the virus
Host immune response : Clears the infection
Our Immune System is like an army
www.avaara.com
•Gradual Change• Due to point mutations in HA and NA• Occurs in both A and B viruses
DRIFT
old neuraminidase new neuraminidase
Drift
http://www.biotech.ubc.ca/db/TEACH/BANK/
PPT/flu2.ppt
•Eight-member Gene Teams” with each member being a separate Player•Promiscuity of the virus – they can give away genes and acquire new segments
Shift – Reassortment of genes
•Occurs through assortment of genes• Sudden change and cause for pandemics• Occurs only in influenza A viruses• We have no pre-existing immunity
Deaths
20% were 10 years old or under
64% were 25 years old or under
87% were 35 years old or under
Median Age 16-20 years old
Avian H5N1 Virus jumped species
2009 Swine H1N1 Flu “You have killed us all”
Death - 17,770 people in 213 countries in 2009
1918 1957 1968 1977 19971998/9
2003
H1
H1H3
H2
H7H5H5
H9
SpanishInfluenza
AsianInfluenza
RussianInfluenza
AvianInfluenza
Hong KongInfluenza
Timeline of influenza infection
2014
Swine H1
“The pandemic clock is ticking, we just don’t know what time it is”
E. Marcuse
• Inactivated vaccine• (generates only antibody response)
• Live attenuated vaccine (generates both antibody and T cell responses)
Annual
Cornerstone of Prevention
Immunology 101
Host response to viral infection
• Antibodies against Hemagglutinin
• CD8 T cells lyse infected cells
• CD4 T cells
surveillance
select strains
prepare reassortants
standardize antigen
assign potency
review/license
formulate/test/package
vaccinate
WHO/CDC)
WHO/CDC/FDA
CDC/FDA
FDA
FDA
FDA
manufacturers
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
clinic
Vaccine Production
Cell SubstratePreparation
Remove Cells,Purify Virus
Infect &Incubate
InactivateVirus
Influenza Vaccine Production
• Selection of strains difficult and time consuming
• Annual, seasonal production
• Technical process, specialized facilities
• Lack of cross protection against antigenic variants Long term protection uncertain ??
• Relatively high cost
• Annual vaccine administration is required26
Constraints of Vaccine Production
Pre-pandemic: Vaccine Planning
• Definition: Vaccines developed against influenza viruses that are currently circulating in animals and that have the potential to cause a pandemic in humans
• Rationale: might provide priming or “limited protection” against pandemic strain Goal: Reduce morbidity or mortality Might not reduce number of viral infections
• Problem: Which vaccine strains, and when should it be given?
27
Despite . . . – Expanded global and national surveillance – Better healthcare, medicines, diagnostics– Greater vaccine manufacturing capacity
New risks:– Increased global travel and commerce– Greater population density– More elderly and immunosuppressed– More daycare and nursing homes– Bioterrorism
Pandemic Flu Today