Tracking and forecasting influenza virus evolution

Trevor Bedford (@trvrb)
4 Apr 2019
Universal Influenza Vaccine Meeting
Wellcome Trust

Seasonal influenza virus evolution

Population turnover of A/H3N2 influenza is extremely rapid

Clades emerge, die out and take over

Clades show rapid turnover

Dynamics driven by antigenic drift

Drift necessitates vaccine updates

H3N2 vaccine updates occur every ~2 years

Vaccine strain selection by WHO

Problem of applied evolutionary biology

Every paper in the field...

  • "These observations have implications for influenza surveillance and vaccine formulation" (Wolf et al 2006)
  • "Our results have implications for the design of vaccines to combat rapidly mutating viral diseases" (Gupta et al 2006)
  • "These results may have important implications for influenza vaccine and antiviral research" (Bhatt et al 2011)
  • "Needless to say, these results have important implications for the updating of vaccines against influenza" (Zinder et al 2013)

Disconnect between evolutionary studies and information needed by WHO

  • WHO needs specific advice, ie this strain is likely to take off, this strain is likely to die out
  • Problems of generality and timeliness

Decided to tackle this head on and build something that

  1. Charts behavior of specific strains
  2. Can be kept continually up to date


Project to provide a real-time view of the evolving influenza population


Project to conduct real-time tracking of pathogen evolution

with Richard Neher, James Hadfield, Emma Hodcroft, Tom Sibley,
John Huddleston, Colin Megill, Sidney Bell, Barney Potter,
Charlton Callender

Up-to-date analysis publicly available at:

Central outputs used by GISRS

  1. Antigenic phenotypes (biweekly selection of ferret sera)
  2. Frequencies (twice yearly selection of vaccine strain)
  3. Forecasts (twice yearly selection of vaccine strain)

Weighted clade frequencies

Forecasts of clade turnover

Ecosystem made possible by open data sharing, a common data model and APIs

Obvious low-hanging issues with current vaccine

Egg-adaptation makes for no good selection

Neuraminidase shows equally rampant adaptive evolution

Feb timing extremely challenging

Immediate improvements to seasonal influenza vaccine platform

  1. Move to pure protein production or RNA vaccine
  2. Incorporate neuraminidase
  3. Pick region-specific vaccine sequence in ~Jun for ~Oct distribution


Bedford Lab: Alli Black, John Huddleston, Barney Potter, James Hadfield,
Louise Moncla, Tom Sibley, Maya Lewinsohn, Katie Kistler

Influenza: WHO Global Influenza Surveillance Network, GISAID, Richard Neher, Barney Potter, John Huddleston, James Hadfield, Dave Wentworth, Becky Garten, Jackie Katz, Colin Russell, Andrew Rambaut, Marta Łuksza, Michael Lässig, Richard Reeve

Nextstrain: Richard Neher, James Hadfield, Colin Megill, Sidney Bell, Charlton Callender, Barney Potter, John Huddleston, Emma Hodcroft