Influenza A virus From biology to

vaccines



Samita Andreansky
Departments 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
Americas deaths from influenza were greater
than the number of U.S. servicemen killed in any
war
0
100
200
300
400
500
600
700
800
900
Civil WWI 1918-19 WWII Korean Vietnam
War Influenza War War
Thousands
0
900
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 persons mouth
and nose when they
cough and sneeze.

Touching objects
contaminated with
particles from an infected
persons 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 persons 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)
Neuraminidase
Hemagglutinin

Type of nuclear
material
Virus
type
Geographic
origin
Strain
number
Year of
isolation
HA and
NA
substrain
Virus Nomenclature
Serotypes in humans

HA 1-16
NA 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
new hemagglutinin old hemagglutinin
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 1997
1998/9
2003
H1
H1
H3
H2
H7
H5
H5
H9
Spanish
Influenza
Asian
Influenza
Russian
Influenza
Avian
Influenza
Hong Kong
Influenza
Timeline of influenza infection
2014
Swine H1
The pandemic clock is ticking, we just
dont 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 Substrate
Preparation
Remove Cells,
Purify Virus
Infect &
Incubate
Inactivate
Virus
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 required

26
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