Molecular evolution of HA gene of the influenza A H1N1 pdm09 strain during the consecutive seasons 2009-2011 in Hangzhou, China: several immune-escape variants without positively selected sites.

Background: Even under immune pressure, the highly active influenza A H1N1 pdm09 variants emerged again in December 2010. Did the variability lead to poor vaccine effectiveness?

Objectives: To study the genetic distance and antigenic drift of the influenza A H1N1 pdm09 strains based on the sequence analysis of HA virus gene segments during consecutive seasons 2009-2011 in Hangzhou, China.

Study Design: 39 Clinical samples from influenza-like-illness patients with culture-confirmed influenza A H1N1 pdm09 infections were collected over seasons in routine influenza surveillance. The HA gene was amplified and sequenced. A perspective analysis of genetic distance, antigenic drift and positively selected sites were conducted.

Results: Analyses of human influenza A H1N1 pdm09 strains isolated in Hangzhou revealed that during the seasons 2009-2011, the antigenic drift had occurred, away from the northern hemisphere 2010/2011 influenza vaccine strain A/California/07/2009. The 2010/2011 viruses cluster in two main branches with a significant genetic distance, characterized by either S202T and S468N, or K180T/I, V216A, P288S, I312V and I389F. Interestingly, the epitopes corresponding to the immune-escape characteristic have altered much, but none of the amino acid substitutions in 2010/2011 variants were positively selected.

Conclusions: The results of genetic surveillance in this study might account for frequent outbreaks of the influenza A H1N1 pdm09 strains since December 2010 and the disappearance after three months circulation. It facilitates early detection of antigenic sites for the virus to escape immunological restraint in 2010/2011 season. Continuous monitoring of antigenic changes is recommended.