Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants

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 P(epitope)–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.