Biophysics and evolution: improving models to predict influenza vaccine effectiveness

25-26 February, 2021
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Virtual meeting via Zoom

Organised by: Professor Olwyn Byron, Dr Will Harvey, Dr Ed Hutchinson and Dr Richard Reeve (University of Glasgow)

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Workshop Overview

​This workshop will discuss new interdisciplinary approaches to aid influenza vaccine strain selection through an improved understanding of the biophysics of influenza virus surface proteins. 
Like many viruses, influenza viruses are infectious because glycoproteins on their surfaces bind to receptors on host cells.  Antibodies that bind these glycoproteins can neutralise the virus, but this is evaded by rapid viral evolution.  This ‘antigenic drift’ necessitates bi-annual updates to the recommended influenza vaccine formulation, and due to the time required to develop new influenza vaccine strains and to manufacture them at scale the evolution of influenza viruses must be predicted months in advance.  Influenza viruses continue to kill hundreds of thousands of people each year and vaccines represent the most important means of disease control.

Predicting the evolutionary success of antigenic variants ideally requires the integration of virus phylodynamics with models of the fitness effects of mutations.  This requires a detailed understanding of the interactions of glycoproteins with cell surface receptors and with antibodies, interactions which are governed by biophysics.  To model the fitness effects of mutations, we must understand not only the impact of mutations on antibody neutralisation, but also their direct impact on glycoprotein structure, function, and receptor interactions.  Biophysics has a role to play both in the assays used to characterise influenza variants and the modelling that supports various components of the vaccine development process.  At present, our ability to make accurate predictions of lineage success is limited.  Despite enormous and sustained global expense and effort, predicting the effectiveness of each influenza vaccine strain under consideration for selection remains challenging.
To address this ongoing global health challenge, this workshop will facilitate discussions between physicists, biophysicists, structural biologists, mathematical modellers, vaccine manufacturers and virologists to support projects that will improve influenza vaccine strain selection and to address the following key questions:
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• What is the physics which underpins the interactions key to infection and the immunological response?
• How can biophysical approaches improve our ability to predict virus-receptor and antibody-receptor interactions?
• Can we utilise new physics-based approaches to facilitate better measurement of these interactions and better modelling?
• How can we better incorporate molecular dynamics and the transience of key interactions into our modelling?
• How do various biophysical interactions linked to the virus genotype contribute to the fitness of an influenza strain?

Who should attend?

Participation in the workshop will be by application and invitation.   We have set a target of roughly 40 participants (including organisers) and will endeavour to attain a gender balance in workshop participants as far as possible.  The primary reason for limiting participation is so to facilitate plenty of effective focussed discussions and breakout sessions which are more effective in smaller groups. The application for participation includes a check-list of expertise so that we can ensure appropriate multi-disciplinarity in the workshop and when assigning participants and speakers to break-out groups. Some talks are aimed at getting participants up to speed on areas with which they may be unfamiliar, so that everyone is on the same page at a basic level by the end of the workshop and so that as the workshop progresses, participants gain in confidence and contribute more freely to discussions. For those unable to make the live event it is intended a recording of talks will be made freely available on YouTube and a published paper will summarise the key challenges in the field.

Provisional Programme

The workshop will be held on two successive afternoons, to facilitate the involvement of colleagues from the US.  All times below are GMT. The goal of the plenary discussion early in the first day will be to identify 5 topics on which to focus the subsequent 5 break-out sessions, each of which will bring together around 6 participants and through which all participants will rotate over the course of the workshop, such that participants engage with a different mix of colleagues at each rotation. 

Day 1	25 February
14.00	Meeting Welcome and introductions from Ed Hutchinson
14.15	Orientation, goals and ice-breaker from Will Harvey
14.30	John Skehel (The Francis Crick Institute) 'Structural biology of influenza virus'
15.00	Plenary discussion - Richard Reeve and Olwyn Byron (University of Glasgow) 'What are the big gaps and challenges?'
15.30	Refreshment Break
15.40	Robb de Vries (Universiteit Utrecht) 'Receptor binding specificity of influenza A virus'
16.10	Affar Karimullah (University of Glasgow) 'New Technology for measuring interactions'
16.25	Breakout session 1
17.05	Refreshment break
17.15	Joshua Sealy (The Pirbright Institute) 'Interactions between receptor-binding, immune evasion and glycan shielding'
17.30	Oliver Dibben (AstraZeneca)'Live attenuated influenza vaccine effectiveness: beyond antigenicity’
17.45	Breakout session 2
18.25	Day 1 wrap up discussion
19.00	Day 1 close

Day 2	26 February
14.00	Recap and re-orientation
14.15	Marta Łuksza ​(Mount Sinai) 'Modelling to predict evolutionary success of influenza lineages'
14.45	Chris Illingworth (University of Cambridge) 'Within-host evolution of acute respiratory viruses'
15.00	​Breakout session 3
15.40	Refreshment break
15.50	Rommie Amaro (University of California, San Diego)  'Biophysical simulations for computational virology'
16.20	​Breakout session 4
17.00	Break out session 5
17.40	Refreshment Break
17.50	Closing discussion - review of the workshop breakouts and drafting of position piece
19.00	Workshop close

Applications for this workshop has now closed. If you would like to get in contact, please email k.h.baker@dur.ac.uk.