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Divergent #antibody-mediated #population #immunity to #H5, #H7 and #H9 subtype potential #pandemic #influenza viruses

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By G.M.

 


Abstract

Influenza continues to cause significant mortality globally and possesses substantial pandemic potential. Assessing pandemic risk requires a clear understanding of existing population immunity. Leveraging a unique large-scale cohort of human sera, we evaluated total and neutralising antibody-mediated immunity to multiple haemagglutinin (HA) proteins, including those from subtypes with high pandemic potential. Our analysis reveals that population immunity is heterogeneous, with distinct age-dependent differences in responses to H5, H7, and H9 avian influenza subtypes. These shifts align with historical circulation patterns of seasonal H1N1 and H3N2 human viruses. Notably, H7 viruses are primarily neutralised through head domain epitopes, while H5 viruses are targeted mainly via stem epitopes, although in both instances some neutralisation occurred via receptor binding site-adjacent epitopes. Furthermore, H7 responses were dominated by non-glycan-targeted IgG2 antibodies, whereas H5 responses were primarily IgG1-mediated. These findings highlight varying levels of susceptibility to influenza across the population, supporting vaccination approaches informed by exposure history.


Competing Interest Statement

CPT has received lecture fees from Moderna.


Funding Statement

J.S.B. was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) doctoral training programme grant [grant number BB/M011224/1]. R.S. is funded by a Medical Research Council Impact Accelerator Account grant [grant ref MR/X502674/1]. RG was funded by The Institute for Global Pandemic Planning at the University of Warwick, UK, as part of a philanthropically supported doctoral programme. K.C. was funded via the Medical Research Council doctoral training programme grant [MC_UP_A025_1011]. L.H. was funded by a Defence and Science Technology Laboratory grant [grant ref RQ31692]. U.O. and C.P.T. acknowledge funding from the British Council ISFP scheme [grant number 47650215]. N.C.R. is supported by a Royal Society Dorothy Hodgkin Research Fellowship [grant number DHR00620].

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.09.08.25335309v1

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