A high content
peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)]
proteome and haemagglutinin
proteins from 12 other
influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum
IgG epitope signatures before and after
Pandemrix(®) vaccination or H1N1
infection in a Swedish cohort during the pandemic
influenza season 2009. A very narrow pattern of pandemic flu-specific
IgG epitope recognition was observed in the serum from individuals who later contracted H1N1
infection. Moreover, the pandemic
influenza infection generated
IgG reactivity to two adjacent
epitopes of the
neuraminidase protein. The differential serum
IgG recognition was focused on
haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu
infections. We further identified a novel
epitope VEPGDKITFEATGNL on the Ca antigenic site (251-265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1
infection (confirmed by
RNA PCR analysis from nasal swabs). This
epitope was mapped to the receptor-binding domain of the
influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased
epitope mapping using
peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1
infection induced a different footprint of
IgG epitope recognition patterns compared with the pandemic H1N1
vaccine.