Abstract
The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated Pepitope–a measure of antigenic diversity based on changes in the epitope regions–for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive.
Highlights
In April 2009, a novel human influenza A(H1N1) virus was identified
Both the nucleotide and amino acid sequences of the coding regions and the sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segment coding regions were obtained from the National Centre for Biotechnology Information (NCBI) influenza virus resource [15]
Epitopes Because of the uncertainty regarding the location of the epitope regions of the hemagglutinin protein, we examined mutations using three different definitions for these regions: (1) a set of epitopes defined by matching the epitopes to H3N2 [5]; (2) a subset of the first set that are natural epitopes [23]; and (3) a set of laboratory confirmed sites for prior seasonal H1N1 strains [24]
Summary
In April 2009, a novel human influenza A(H1N1) virus was identified This virus rapidly spread around the globe causing significant morbidity and mortality in 2009/2010. Except for the elderly, the vast majority of individuals around the world did not have protective immunity against the virus and were susceptible to infection [4]. This relatively low immunological pressure has presumably contributed to the fact that there has been only limited antigenic change in the virus. Evidence from equine and human challenge studies [6] suggest that reinfection probability increases as the number of amino acid differences between the primary infection/vaccine strain and the challenge strain increase. In vitro studies of the A(H1N1)pdm strain have shown that only one or two amino acid changes can reduce the ability of human sera to bind viruses of this strain [8]
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