H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus pandemrix(®) -vaccination

A high content peptide microarray containing the entire Influenza A virus (A/California/08/2009(H1N1)) proteome and hemagglutinin proteins from 12 other influenza A subtypes, including the hemagglutinin from the (A/South Carolina/1/1918(H1N1)) strain, was used to gauge serum IgG epitope signatures prior to 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 hemagglutinin 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 hemagglutinin, 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 hemagglutinin (HA) 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, it also shows that H1N1 infection induced a different footprint of IgG epitope recognition patterns as compared to the pandemic H1N1 vaccine. This article is protected by copyright. All rights reserved.