What drives antigenic drift in a single influenza season?

1
What drives antigenic drift in a single influenza
season?
Maciej F. BoniStanford University, Department of
Biological SciencesCo-authors Julia R. Gog,
Viggo Andreasen, Marcus W. Feldman
DIMACS Workshop on the Epidemiology and Evolution
of Influenza Rutgers University, January 26, 2006
2
Flu epidemics and antigenic drift
weekly illnesses/10,000 inhabitants (NL)
20
( focus will be on HA1 )
1996
1997
1998
de Jong et al (2000)
3
HA1 polymorphism local datasets

• Coiras et al, Arch. Vir. (2001)
• Schweiger et al, Med. Microbiol. Immunol. (2002)
• Pyhälä et al, J. Med. Virol. (2004)

mean within-season distance 2.8 aa (6nt) max
within-season distance 8 aa (25nt)
4
Neutral Epidemic Model
5
Neutral Epidemic Model
6
Strain frequencies are Poisson-distributed
Frequency of strain k
Mean number of mutations per virus moves forward
in time according to a molecular clock.
7
Modeling antigenic drift and immunity
the epidemic-originating strain
-2
-1
0
1
2
3
4
8
Modeling antigenic drift and immunity
the epidemic-originating strain
-2
-1
0
1
2
3
4
Distance between immunizing strain and
challenging strain determines level of
cross-immunity. We model this as an infectivity
reduction and say it wanes exponentially with
distance
9
Non-neutral model

• Amino-acid replacements in influenza surface
  proteins confer a fitness benefit via increased
  transmissibility
• Hosts have some immunity structure from
  vaccination or previous infections
• ( need both )

10
Keeping track of hosts
q0 completely immune ( to I0 )
q30 completely naive
11
Keeping track of variables
12
Equations
13
Equations
14
Equations
fitness of strain k
15
Population genetics
Define mean antigenic drift in virus population
as
This is the Price Equation, thus, the basic
influenza population dynamics can be viewed in a
standard population genetic framework.
16
Under neutrality
17
I(t)
18
Define the excess antigenic drift as
How do you know when the epidemic ends?
19
I(t)
20
In general, how do the parameters affect the
model results?
21
Partial correlations
immunity
immune-escape/mutation
22
Partial correlations
immunity
immune-escape/mutation
23
Host immunity drives antigenic drift
24
Public health implications

• Vaccination strategies under-vaccination or
  imperfect vaccination may cause much excess
  antigenic drift.
• Pandemic implications need to consider the
  effects of vaccination during the 2nd year after
  a pandemic, and their effects on the 3rd year
  after a pandemic.

25
Thanks

• Viggo Andreasen
• University of Roskile, Department of Mathematics
  and Physics
• Julia Gog
• Cambridge University, Department of Zoology
• Marc Feldman
• Stanford University, Department of Biological
  Sciences
• Freddy Christiansen
• University of Aarhus, Department of Biology
• Mike Macpherson
• Stanford University, Department of Biological
  Sciences

26
(No Transcript)