Completed Infection & Immunity Genetics & Molecular Biology

The evolution of influenza virus: studies of within host and between host evolution to improve pandemic risk assessment and vaccine updates.

Funder Wellcome Charity-funded
Recipient organisation Imperial College London
Funding £1.3M
Period Jan 2016 — Jun 2021

In plain English

AI plain-English summary

Every year, influenza viruses mutate just enough to slip past our immune defences, forcing a new vaccine update. This project aims to understand exactly how those mutations happen—both inside a single infected person and as the virus spreads through a population—so that public health officials can better predict which strains pose the greatest pandemic threat. The problem is that transmissibility, the key trait that turns a bird flu into a human pandemic, is currently measured using ferret experiments that have known limitations. The researchers will develop new laboratory, mathematical, and bioinformatic methods to quantify transmissibility more accurately. They will compare H7N9 viruses circulating in poultry with the 1968 H3N2 pandemic virus, reconstructing the avian precursor and testing how key genetic changes altered its ability to spread. They will also track how the H3N2 virus evolved seasonally between 2007 and 2009, comparing that to its pandemic emergence. If successful, this work will provide a probabilistic framework for predicting antigenic drift—the process that forces annual vaccine updates. That could make vaccine strain selection faster and more reliable, and improve risk assessments for non-human influenza strains before they jump to people.

View original technical description
The evolution of Influenza A viruses poses substantial public health challenges through pandemics and the continual evolution of seasonal strains. Transmissibility is a key phenotype of influenza A virus evolution and, despite a number of methodological shortcomings, is measured most frequently by ferret transmission experiments. We will develop novel laboratory, mathematical, and bioinformatic methods to accurately quantify the transmissibility of influenza viruses. We will compare non-human H7N9 viruses, that currently circulate in poultry and occasionally zoonose to humans, to the successfully emergent 1968 H3N2 pandemic virus. We will infer the avian precursor to the 1968 pandemic virus and measure its transmissibility and that of likely key intermediates by synthesizing hemagglutinin (HA) variants. We will develop novel laboratory and bioinformatic approaches to measure within-host evolution and thus quantify within- and between-host evolutionary trajectories. We will use the same techniques to compare the seasonal evolution of H3N2 HA during the period 2007 to 2009 with its pandemic emergence. Our results will: increase fundamental understanding of the key phenotypes of the HA gene, improve our ability to risk assess non-human strains, and provide a probabilistic framework with which to predict antigenic drift.

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Researchers

Wendy Barclay (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Evolution of modern H3N2 influenza A viruses
Quantifying pandemic risk caused by within-host evolution of influenza A/H5N1 viruses
Mechanistic and Pathway Analysis of Animal Influenza Virus cross-species transmission by constructing genotype and phenotype networks
Understanding the Molecular Features of Novel Emergent (H9Nx and H7Nx) Avian Influenza Viruses Posing Zoonotic and Pandemic Threats
An integrated approach to understanding the evolutionary, antigenic and epidemiological dynamics of human influenza virus.

Original classification

Collaborative Award in Science

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