Tracking influenza antigenic evolution and geographic circulation
Trevor Bedford (@trvrb)
27 Jun 2016
Microbiology Department Seminar
Korea University College of Medicine
Slides at bedford.io/talks/
Influenza virus
Influenza H3N2 vaccine updates
Gene flow and population turnover
Turnover can be seen in the flu phylogeny
Flu pandemics caused by host switch events
Influenza B does not have pandemic potential
Phylogenetic trees of different influenza lineages
Antigenic evolution drives viral dynamics
Influenza hemagglutination inhibition (HI) assay
HI measures cross-reactivity across viruses
Data in the form of table of maximum inhibitory titers
Compiled HI data difficult to work with
Antigenic cartography positions viruses and sera to recapitulate titer values
Antigenic cartography positions viruses and sera to recapitulate titer values
Schematic HI table and antigenic map
Bayesian multidimensional scaling (BMDS)
Integration through Markov chain Monte Carlo (MCMC)
Antigenic map of H3N2 influenza from 1968 to 2011
Antigenic drift of H3N2 influenza
Factoring the BMDS model
Phylogeny of H3N2 virus sequences
Modeling continuous characters via Brownian motion
Including diffusion in MDS model
Factoring the BMDS diffusion model
Antigenic cluster transitions
with Charles Cheung, Andrew Rambaut and Marc Suchard
Cheung et al 2015. Detailed antigenic dynamics of influenza virus revealed by Bayesian phylogenetic clustering. In prep.
Factoring the BMDS discrete transition model
H3N2 discrete antigenic dynamics
Association map of H3N2 antigenic clustering
H3N2 driver mutations
Sites: 135, 144, 145, 155, 156, 157, 158, 159, 189, 223 , 225, 226
H3N2 clustering with driver mutations
Phylogenetic trees of different influenza lineages
Antigenic phenotype across lineages
Antigenic drift across lineages
Antigenic drift across lineages
Seasonality in influenza
Hypotheses of influenza circulation patterns
Influenza H3 genealogy for NY state viruses
Hypotheses of influenza circulation patterns
Sample H3N2 from around the world
Treating geographic state as an evolving character
Phylogeny of H3 with geographic history
Infer geographic transition matrix
Air travel predicts migration rates
Geographic location of phylogeny trunk
Region-specific ancestry
Phylogenies across subtypes / lineages
H3N2 phylogeny
H1N1 phylogeny
B/Vic phylogeny
B/Yam phylogeny
Ancestry patterns across lineages
Regional persistence patterns
How to explain these differences?
Age distribution across viruses
Air travel differences between adults and children
Epidemiological model of varying rates of antigenic drift
Results of varying antigenic drift
Interaction between virus evolution, epidemiology and human behavior drives migration rate differences
Circulating antigenic variants
Vaccine strain prediction
Antigenic evolution in H3N2
Vaccine strain selection timeline
Predictive models
A simple predictive model estimates the fitness $f$ of virus $i$ as
$$\hat{f}_i = \beta^\mathrm{ep} \, f_i^\mathrm{ep} + \beta^\mathrm{ne} \, f_i^\mathrm{ne}$$
where $f_i^\mathrm{ep}$ measures cross-immunity via substitutions at epitope sites and $f_i^\mathrm{ep}$ measures mutational load via substitutions at non-epitope sites.
Predictive models
Another approach quantifies phylogenetic branching patterns
nextflu
Project to provide a real-time view of the evolving influenza population
All in collaboration with Richard Neher
nextflu
pipeline
- Download all recent HA sequences from GISAID
- Filter to remove outliers
- Align sequences
- More filtering
- Build tree
- Estimate frequencies
- Export JSON for visualization
Acknowledgements
Richard Neher (Max Planck Tübingen), Andrew Rambaut (University of Edinburgh),
Colin Russell (Cambridge University), Charles Cheung (Fred Hutch),
Marc Suchard (UCLA), Steven Riley (Imperial College),
Philippe Lemey (Philippe Lemey (KU Leuven), Gytis Dudas (University of Edinburgh)
WHO Global Influenza Surveillance Network / GISAID: Ian Barr, Shobha Broor, Mandeep Chadha, Nancy Cox, Rod Daniels, Palani
Gunasekaran, Aeron Hurt, Anne Kelso, Alexander Klimov, Nicola Lewis, Xiyan Li, John McCauley, Takato Odagiri, Varsha Potdar, Yuelong Shu, Eugene Skepner, Masato Tashiro, Dayan Wang, Xiyan Xu
Contact
- Website: bedford.io
- Twitter: @trvrb
- Slides: bedford.io/talks/flu-dynamics-korea-university/