Minor Changes in the Hemagglutinin of Influenza A(H1N1) 2009 Virus Alter Its Antigenic Properties

Background: The influenza A(H1N1) 2009 virus has been the dominant type of influenza A virus in Finland during the 20092010 and 2010-2011 epidemic seasons. We analyzed the antigenic characteristics of several influenza A(H1N1) 2009 viruses isolated during the two influenza seasons by analyzing the amino acid sequences of the hemagglutinin (HA), modeling the amino acid changes in the HA structure and measuring antibody responses induced by natural infection or influenza vaccination. Methods/Results: Based on the HA sequences of influenza A(H1N1) 2009 viruses we selected 13 different strains for antigenic characterization. The analysis included the vaccine virus, A/California/07/2009 and multiple California-like isolates from 2009-2010 and 2010-2011 epidemic seasons. These viruses had two to five amino acid changes in their HA1 molecule. The mutation(s) were located in antigenic sites Sa, Ca1, Ca2 and Cb region. Analysis of the antibody levels by hemagglutination inhibition test (HI) indicated that vaccinated individuals and people who had experienced a natural influenza A(H1N1) 2009 virus infection showed good immune responses against the vaccine virus and most of the wild-type viruses. However, one to two amino acid changes in the antigenic site Sa dramatically affected the ability of antibodies to recognize these viruses. In contrast, the tested viruses were indistinguishable in regard to antibody recognition by the sera from elderly individuals who had been exposed to the Spanish influenza or its descendant viruses during the early 20(th) century. Conclusions: According to our results, one to two amino acid changes (N125D and/or N156K) in the major antigenic sites of the hemagglutinin of influenza A(H1N1) 2009 virus may lead to significant reduction in the ability of patient and vaccine sera to recognize A(H1N1) 2009 viruses.