Immunity and vaccination to Influenza H1N1 swine flu

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Immunity and vaccination to InfluenzaH1N1
swine flu
Mohammad S. Khalifeh Assistant Professor,
Immunobiology Department of Veterinary Basic
Medical Science Department of Molecular Biology
and Genetic Engineering Jordan University of
Science and Technology Technical
consultant Jordan biological Diagnostics Jorda
n Bio-industrial Center (JOVAC)
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KNOWLEDGE IS OUR BEST DEFENSE
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The principle immunity to infection
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The principle immunity to infection
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Mechanisms of adaptive and innate immunity
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Influenza Genes

• Influenza A viruses have 8 gene segments that
  encode 10 polypeptides
• Segment 1 (2,341 nt) PB2 (RNA transcriptase)
• Segment 2 (2,341 nt) PB1 (RNA transcriptase)
• Segment 3 (2,233 nt) PA (RNA transcriptase)
• Segment 4 (1,778 nt) HA (hemagglutinin) - 16
  known subtypes
• Segment 5 (1,565 nt) NP (nucleoprotein)
• Segment 6 (1,413 nt) NA (neuraminidase) - 9
  known subtypes
• Segment 7 (1,027 nt) M1, M2 (matrix proteins)
• Segment 8 (890 nt) NS1, NS2 (inhibits mRNA
  splicing and IFN response nuclear export signal
  for viral RNPs)

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Immunity to Influenza Virus
Neutralization
Y
Y
Y
Antibody-mediated Opsonization
Y
Y
Y
Y
Y
HA
Heterotypic Abs react with proteins of influenza
Virus rather than HA and NA
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Whats the Problem?!!!
Immunopathogenesis and genetics
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Type A Influenza Viruses

• Identified by 2 Surface Protein Structures
• Combinations
• H - Hemagglutinin (1 16)
• Entry into Cell
• N - Neuraminidase ( 1- 9)
• Exit from Cell
• 144 Possible combinations

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Antigenic Drift
Mutation
H1N1
H1N1
H1N1

• Imperfect manufacturing of virus
• Small changes in H and N
• Partial immunity in population
• Incomplete protection still get sick
• Need new flu vaccine every year

This One I Know.. But
Yearly epidemics occur
H1N1
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Antigenic Shift
H1N1
H1N1
H1N1
H1N1
H1N1
Drives the occurrence of a pandemic
Black is my favorite I am Color blind
H1N1
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Feedback inhibition Vs Heterotypic Abs
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Will a current flu vaccine protect me from Swine
Flu?
Answer No

• Vaccines containing the 200809 trivalent vaccine
  virus strains include
• A/Brisbane/59/2007 (H1N1),
• A/Brisbane/10/2007 (H3N2), and
• B/Florida/4/2006
• All 3 vaccine virus strains were changed for the
  2008-2009 season

2007-2008 Vaccine Strains A/Solomon
Islands/3/2006 (H1N1), A/Wisconsin/67/2005
(H3N2), and B/Malaysia/2506/2004 viruses
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Influenza Vaccines

• Inactivated (TIV)
• intramuscular
• trivalent
• contains egg protein
• Live attenuated vaccine (LAIV)
• intranasal
• trivalent
• contains egg protein

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Inactivated Influenza Vaccine Efficacy

• Duration of immunity for inactivated influenza
  vaccine is considered to be 1 year or less
• The vaccine is actually effective two weeks after
  the shot is given.
• 70-90 effective among healthy persons
  lt65 years of age
• 30-40 effective among frail elderly
  persons
• 50-60 effective in preventing
  hospitalization
• 80 effective in preventing death

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A pandemic soon.. Will A Vaccine Be Easy to
Produce?

• There will be little or no vaccine until 6 - 9
  months after the outbreak begins
• Production process is slow
• 3-6 months until first doses are available
• Longer until enough to cover all high-risk groups
  and general population
• For seasonal influenza, viruses are grown in
  chicken eggs for 7 days to produce high-enough
  titers for vaccines
• Avian influenza viruses kills eggs in 4.5 days
• An insufficient titer is generated for vaccines
• The worlds annual vaccine capacity is 300
  million doses

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Challenges

• Vaccine Supply (annual uncertainty)
• Recommendation vs. prioritization of high-risk
  groups
• Vaccine Distribution (pre-booking)
• Vaccine delivery
• Vaccine Funding and over-reliance on public health

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Live Attenuated Influenza Vaccine (LAIV)

• Approved only for healthy persons 2 years through
  49 years of age who are not pregnant
• healthcare personnel
• persons in close contact with high-risk groups
• persons who want to reduce their risk of
  influenza

MMWR 200857 (RR-7)
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Influenza Vaccination

• Influenza activity can occur as early as October
• Continue to vaccinate throughout influenza season
  (December-March)
• Pregnancy and Influenza Vaccine

MMWR 200857 (RR-7)
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It would be better to have an immunization
program without an epidemic than an epidemic
without an immunization program. (CDC, 1976)
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USA guidelines for vaccine priority groups?

• Tier 1 A Vaccine Producers direct care medical
  workers
• B Persons gt 65 with compromising conditions
• C Pregnant women Household contacts of
  compromised persons
• D Public health emergency responders and
  key public officials.
• Tier 2 A Healthy 65 and older and children
• B Emergency response, essential services
• Tier 3 Key government and society leaders
• Tier 4 Healthy Persons

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The only thing more difficult than planning would
be explaining why you did not do it! -- Marja
Esveld Healthcare Inspectorate, The Netherlands
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Cold vs. Flu (influenza)
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WHO Phases of a Pandemic
Current level
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Lab Testing

• Preferred specimen nasopharyngeal/nasal swab,
  wash, aspirate
• Rapid influenza tests
• Results within 30 minutes
• May determine type (A vs. B)
• High false negative results (30)
• Viral culture
• Results in 3-10 days
• Determine specific subtype or strain
• reference standard of diagnosis
• Not necessary to test all patients
• May not affect clinical decision-making
• Expensive
• Labor intensive
• Cohort hospitalized patients
• Outbreaks