NATS 1670 Study Guide - Final Guide: Live Attenuated Influenza Vaccine, Avian Influenza, Rna-Dependent Rna Polymerase

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Tuesday March 1st, 2016
Pneumonia and Influenza Mortality
- Seasonal Flu – common and occurs every year
- The flu is the most common in winter and fall seasons rather than spring and
summer
- In 2004, a vaccine for the flu wasn’t readily prepared for the “flu season”
- 15th century Italian scholars described the disease as “malathia influenza per
le stele”
A disease influenced by the stars
- The 1918 Spanish Flu Pandemic
Most well known pandemic in 1918 – 1919 high incidence rate of the
flu
Approximately 50 million deaths worldwide
Annual Incidence of Influenza
- Flu Pandemic – situation that the virus is affecting us in an aggressive way all
over the world and goes back to normal after 2- 3 years
Why 1918 Influenza Pandemic has killed a Disproportionate Number of Young
Adults?
- “Cytokine storm” – an immune system that has over-reacted and is damaging
the body, causing failure of multiple organ systems
- Able to transfer the virus to mice; was viewed as an ethical “subject” to test
on
- In this case, a healthy immune system may have been a liability rather than
an asset
- A phenomenon that repeats itself in H5N1 and the 2009 swine H1N1
influenza
- H5N1 = have had since 1997 (affect us directly form chickens to humans and
not really from human to human transmission) 60% are most likely to die
- Swine Flu “H1N1” – young adults was affected the most and it was a human-
to-human transmission spread. Made vaccines on time = pandemic year =
less people were killed
Influenza Virus
- RNA virus
- Consist of 8 RNA segments
- Two proteins
Haemagglutinin (HA)
Attachment protein
Neuraminidase (NA)
Active at the end of the life cycle of the virus
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How can we use the HA and NA against the virus?
- We can make drugs
Neuraminidase can be stopped by Oseltamivir (Tamiflu)
- We can make antibodies that will react with NA and HA
Normally, when we are infected with a virus or vaccinated against a
virus, our specific immunity will be activated and we will not become
infected at the second exposure
However, the virus that re-infects us must be the same as the
first virus of vaccination
Genetic changes
Antigen drifts (seasonal flu)
Antigen shifts (pandemic flu)
- Structure of NA binds to sialic acid
Thursday March 3rd, 2016
- The virus from last year is not going to be the same for this year, therefore
vaccine is not useful
Antigen Drifts in Influenza Virus is Induced by High Mutation Rates
- RNA virus consists of 8 segments
The influenza is an RNA virus
RNA dependent RNA polymerase is not linked to a significant
proofreading mechanism
High error rate of about 1:5,000 nucleotides
Antigen Drift
- In influenza types A, B and C
- High mutation rate in RNA viruses causes gradual changes
HA and NA accumulate mutations (minor antigen change)
- Immune response no longer protects fully
- Sporadic outbreaks, limited epidemics
- Why we need a new vaccine each year, last year virus is going to be different.
Even if you get infected (viruses changes each year)
- Epidemic more causes in a specific region with greater frequency
- Pandemic infection that takes place in the southern and northern
hemisphere
Antigen Shifts
- (Haemagglutinin – HA) H2N2, H5N1 (Neuraminidase – NA)
- Influenza type A only
- Major antigenic change
New subtype (> 15% different) of HA or/and NA proteins
Pre-existing antibodies do not protect
No preexisting immunity
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- May lead to pandemics
- Antigen shifts lasts about 100 years
- Past antigenic shifts with pandemics
1918 – H1N1 “Spanish Influenza” (50 million deaths)
1957 – H2N2 “Asian Flu” (1 – 2 million deaths)
1968 – H3N2 “Hong Kong Flu” (700,000 deaths)
What is the possible mechanism for antigenic shifts?
- Natural hosts of influenza type A viruses
- 6 HA subtypes occur in nature (in birds)
- Human and pigs can host H1, H2, H3
- At least 9 NA subtypes occur in nature (in birds)
- Human and pigs can host N1, N2
Influenza Epidemiology
- Epidemics
Epidemics of influenza A and B arise through antigenic drifts as a
result of several mutations
- Pandemics
Influenza A pandemics arise when a virus with a new
hemagglutinin/neuraminidase, subtype emerges as a result of
antigenic shifts
As a result, the population has no immunity against the new strain
Tuesday March 8th, 2016
Swine Influenza A (H1N1) 2009
- Human to human transmission
- Affect younger age group than that seen during seasons epidemics
- Increased risk of severe or fatal illness in pregnant women when infected
with H1N1 pandemic virus
Theories Behind Antigenic Shift
- Reassortment of the HA and NA genes between human and avian influenza
viruses through third host
- Occurred possibly in 1957 H2N2, the 1968 H3N2 and 2009 H1N1 pandemics
Antigenic Changes in Influenza Virus
- Antigenic drift – mutations (RNA genes)
- Antigenic shift – reassortment (segmented genome)
- 16 HA subtypes and 9 NA subtypes occur in nature
- Until 1997 – only viruses of H1, H2 and H3 known to infect and cause disease
in humans
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Document Summary

Seasonal flu common and occurs every year. The flu is the most common in winter and fall seasons rather than spring and summer. In 2004, a vaccine for the flu wasn"t readily prepared for the flu season . 15th century italian scholars described the disease as malathia influenza per le stele . Most well known pandemic in 1918 1919 high incidence rate of the flu. Flu pandemic situation that the virus is affecting us in an aggressive way all over the world and goes back to normal after 2- 3 years. Why 1918 influenza pandemic has killed a disproportionate number of young. Cytokine storm an immune system that has over-reacted and is damaging the body, causing failure of multiple organ systems. Able to transfer the virus to mice; was viewed as an ethical subject to test on. In this case, a healthy immune system may have been a liability rather than an asset.

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