Researchers from Germany and the United Kingdom have improved the methods of predicting which flu virus strains to include in a given year’s seasonal vaccine by determining which strains were most successful, and which least, at expanding into an entire population.
The team analyzed the DNA sequences of thousands of 1971 influenza A (H3N2) strains isolated from patients worldwide between 1969 and 2007. Using a new statistical method, researchers found that many more mutations succeed in replicating and surviving than was initially believed. These mutations compete; some make it into the entire population, others die out.
“We find that influenza evolves by clonal interference. That is, its adaptation is limited not by the supply of beneficial mutations, but by their competition,” the researchers wrote in their study, published today in the journal Genetics.
That competition, the scientists added, is a ‘red queen’ or continuous-adaptation race between viral strains with different beneficial mutations: “We find an average of at least one strongly beneficial amino acid substitution per year, and a given selective sweep has three to four driving mutations on average.”
The inference of selection and clonal interference, they said, is based on frequency time series of single-nucleotide polymorphisms obtained from a sample of influenza genome sequences over the 39-year period addressed by the study.
Influenza A survives through adaptive changes occurring primarily in antigenic epitopes, the antibody-binding domains of the viral hemagglutinin. The process involves recurrent selective sweeps, during which clusters of simultaneous nucleotide fixations in the hemagglutinin coding sequence are observed about every four years.
The virus analysis is designed to enable scientists to predict trends which can help vaccine developers understand the rules of flu virus evolution.
"Although this study is some distance from direct applications, it is a necessary step toward improved prediction methods. We hope that it helps yield better vaccines against influenza," Michael Lässig, Ph.D., of the Institute for Theoretical Physics at the University of Cologne in Köln, Germany, said in a statement.
Dr. Lässig co-authored the study with Natalja Strelkowa of Imperial College London.