The role of cross-immunity and vaccines on the survival of less fit flu-strains

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The role of cross-immunity and vaccines on the
survival of less fit flu-strains

• Miriam Nuño
• Harvard School of Public Health
• Gerardo Chowell
• Los Alamos National Laboratory
• Xiaohong Wang, Carlos Castillo-Chavez
• Arizona State University

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Flu Epidemic and Pandemic Events

• 1918 Spanish Flu (H1N1) 500,000 deaths in US
  and 20 million
• worldwide.
• 1957 Asian Flu (H2N2) 70,000 deaths in US.
• 1968 Hong Kong Flu (H3N2) 34,000 deaths in US.
• 1976 Swine Flu Scare (H1N1 related??)
• 1977 Russian Flu Scare (H1N1 related)
• 1997 Avian Flu Scare (H5N1, human
  human)

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The Reservoirs of Influenza A Viruses
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What characterizes a successful invader?

• The establishment of an existing strain
• Quarantine
• The role of cross-immunity
• The likelihood of coexistence
• Phenotypic diversity
• Invasion under sub-threshold condition

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Cross-immunity?
Infection with an influenza subtype A strain may
provide cross protection against other
antigenically similar circulating strains

• Little evidence support the existence of
  cross-immunity between
• influenza A subtypes
• Houston and Seattle studies show that
  cross-immunity
• exists between strains within the same subtype.

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Experimental Evidence of cross-immunity

• 1974 Study lt 3 With Prior
• A/HONG KONG/68 (H3N2) OR
• A PRIOR A/ENGLAND/72 (H3N2)
• GOT A/PORT CHALMERS/73
• vs.
• 23 With NO Prior Experience
• 1976 Appearance of A/VICTORIA/75 (H3N2)
• Relative Frequency of First Infected/Previously
  Infected
• (By Another Strain of H3N2 was
  approximately 59)

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Experimental Evidence of cross-immunity

• 1977 Co-circulating H1N2 strains
• Individuals born before 1952 GOT a strain
  of H1N1
• DETECTION OF ANTIBODY-POSITIVE SERA
• YOUNG Changed From 0 to 9.
• OLDER Did not change (remained at 9)
• 1982 (Glezen) No Cross-Immunity Between
  Subtypes
• (H1N1 H3N2)

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Cross-immunity Summarized

• Exhibits subtype specificity
• Exhibits cross-reactivity to variants within a
  subtype, but with reduced cross-reactivity for
  variants that are anti-genically distant from the
  initial variant
• Exhibits a duration of at least five to eight
  years
• Be able to account for the observation that
  resistance to re-infection with H1N1 may last 20
  years

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Model
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Cross-immunity in the model ( )
Measure of the average reduced susceptibility to
Strain j gained by a host after recovery with
Strain i.

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Flu Invasion Conditions (Nuño et al.,)
Pathogens invasion determined by where
, the mean transmission
rate for Strain i is denoted by
while describes the mean
infectious period of strain i . Invasion of a
fully susceptible population is ONLY possible
when
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Flu Invasion and Coexistence
measures the ability of strain 2 to invade a
strain-1 endemic population
Number of secondary cases that strain-2 infected
individuals generate in the susceptible
fraction (primary infection)
Number of secondary cases generated by strain-2
infected individuals among the partially immune
proportion (secondary infection)
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Uncertainty and Sensitivity Analysis of the
Invasion Reproductive Number
(1)
Uncertainty analysis of quantities its
variability generated from the uncertainty of
the input parameters in (1).
Sensitivity Analysis evaluates the relative
impact of to changes in the parameters
in (1).
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Model Parameters and Distributions
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Uncertainty Analysis
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Sensitivity Analysis
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Contribution of to Coexistence
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Immune-specific Contributions to Coexistence
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Estimation of the Contribution of to
Coexistence
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Estimation of the Contribution of to
Coexistence
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Conclusions Future Direction

• Invasion and coexistence are possible when the
  level of cross-immunity is moderate, even under
  sub-threshold condition.
• Cross-immunity reduces the likelihood of
  invasion.
• Transmission rate is the most sensitive parameter
  in (positively correlated)
• Study the role of quarantine on invasion and
  coexistence

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Acknowledgement

• NIH, NSF, MTBI and SAMSI