H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix^® vaccination

Abstract

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.

Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes

“…Overall, amino acid changes which originated as low-frequency variants in antigenic sites represented 50% (2 out of 4) of the total amino acid changes that emerged in antigenic sites of HA sequences during the study period. In NA, only five (out of a total of 144 LFVs) were in the NA antigenic site located within amino acids 141-155 [57]. These included R152 and Y155 in the active site and framework, respectively which have been previously reported to be associated with reduced sensitivity to NAIs.…”

Autoimmunity in narcolepsy

“…Further, Giannoccaro et al failed to establish conclusively the presence of anti-HCRTR2 antibodies in narcolepsy cases [63] and we have found anti-HCRTR2 antibodies in 4 narcolepsy cases out of 80 narcolepsy patients using three different quantification methods (unpublished). Interestingly, it appears that Pandemrix ® vaccine induced a qualitatively different humoral response in vaccinated individuals as compared to individuals after a natural pandemic influenza infection [64] suggestive of differential immune response to the vaccine and a natural infection.…”

Peptide microarray-based characterization of antibody responses to host proteins after bacille Calmette–Guérin vaccination

“…The peptide microarray data analysis was performed according to established protocols [18][19][20][21][22] and novel approaches, as outlined in the sections below.…”