PT  - JOURNAL ARTICLE
AU  - Dennis E. te Beest
AU  - Erwin de Bruin
AU  - Sandra Imholz
AU  - Marion Koopmans
AU  - Michiel van Boven
TI  - Heterosubtypic cross-reactivity of HA1 antibodies to influenza A, with emphasis on nonhuman subtypes (H5N1, H7N7, H9N2)
AID  - 10.1101/116327
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 116327
4099  - http://biorxiv.org/content/early/2017/03/13/116327.short
4100  - http://biorxiv.org/content/early/2017/03/13/116327.full
AB  - Epidemics of influenza A vary greatly in size and age distribution of cases, and this variation i attributed to varying levels of pre-existing immunity. Recent studies have shown that antibody mediated immune responses are more cross-reactive than previously believed, and shape patterns of humoral immunity to influenza A viruses over long periods. Here we quantify antibody responses to the hemagglutinin subunit 1 (HA1) across a range of subtypes using protein microarray analysis of cross-sectional serological surveys carried out in the Netherlanc before and after the A/2009 (H1N1) pandemic. We find significant associations of responses, both within and between subtypes. Interestingly, substantial overall reactivity is observed to HA1 of avian H7N7 and H9N2 viruses. Seroprevalence of H7N7 correlates with antibody titer to A/1968 (H3N2), and is highest in persons born between 1954 and 1969. Seroprevalence of H9N2 is high across all ages, and correlates strongly with A/1957 (H2N2). This correlation is most pronounced in A/2009 (H1N1) infected persons born after 1968 who have never encountered A/1957 (H2N2)-like viruses. We conclude that heterosubtypic antibody crossreactivity, both between human subtypes and between human and nonhuman subtypes, is common in the human population.