Abstract Title
Genetic relatedness between emerging zoonotic and human-adapted influenza A viruses since 1918: consolidated pairwise identity analyses to inform potential cross-reactivity
Abstract
Background: Cross-reactive antibodies against the hemagglutinin (HA) and/or neuraminidase (NA) surface proteins of human-adapted influenza A viruses (IAVs) may prevent, reduce severity and/or modify the age-related risk of emerging zoonotic IAV. To inform potential cross-reactivity, we performed a sweeping and consolidated analysis of HA and NA relatedness between recent human-zoonotic and established human-adapted IAVs since 1918.
Methods: We compared percent amino-acid pairwise identities in matched extracellular domains of the HA1-head, HA2-stalk and NA-head of representative human-zoonotic (H5N1, H5N6, H5N8, H9N2, and H7N9) against all human-adapted (H1N1, H2N2 and H3N2) IAV within GISAID from 1918 through 2024, interpreting also in relation to phylogenetic grouping (Gp).
Results: In all comparisons between human-adapted H1 (Gp1), H2 (Gp1) or H3 (Gp2) and human-zoonotic H5 (Gp1), H9 (Gp1) or H7 (Gp2) viruses, HA1-head identities were <60%, except H5 vs. H2 (65-70%). HA2-stalk identities relative to H1/H2 or H3 were for H5: >80% and <60%; for H9: <65% and <65%; and for H7: <60% and ~65%, respectively. Homosubtypic NA-head exceeded HA2-stalk identities for H5N1 relative to H1N1 (>85%, especially vs. 1918 and 2009 pandemic strains (>90%)) and for H9N2 vs. H2N2 or H3N2 (>80%). Heterosubtypic NA identities were otherwise <50%.
Conclusions: The overall and age-related risk of zoonotic influenza may be modified by immunological cross-reactivity conferred by exposure to human-adapted IAV. Given identities >80% in the HA2-stalk and NA-head of emerging H5N1 vs. circulating H1N1, and in the homosubtypic NA of H9N2 vs. H3N2, the potential role of cross-reactivity in both domains warrants further immuno-epidemiological investigation.
Methods: We compared percent amino-acid pairwise identities in matched extracellular domains of the HA1-head, HA2-stalk and NA-head of representative human-zoonotic (H5N1, H5N6, H5N8, H9N2, and H7N9) against all human-adapted (H1N1, H2N2 and H3N2) IAV within GISAID from 1918 through 2024, interpreting also in relation to phylogenetic grouping (Gp).
Results: In all comparisons between human-adapted H1 (Gp1), H2 (Gp1) or H3 (Gp2) and human-zoonotic H5 (Gp1), H9 (Gp1) or H7 (Gp2) viruses, HA1-head identities were <60%, except H5 vs. H2 (65-70%). HA2-stalk identities relative to H1/H2 or H3 were for H5: >80% and <60%; for H9: <65% and <65%; and for H7: <60% and ~65%, respectively. Homosubtypic NA-head exceeded HA2-stalk identities for H5N1 relative to H1N1 (>85%, especially vs. 1918 and 2009 pandemic strains (>90%)) and for H9N2 vs. H2N2 or H3N2 (>80%). Heterosubtypic NA identities were otherwise <50%.
Conclusions: The overall and age-related risk of zoonotic influenza may be modified by immunological cross-reactivity conferred by exposure to human-adapted IAV. Given identities >80% in the HA2-stalk and NA-head of emerging H5N1 vs. circulating H1N1, and in the homosubtypic NA of H9N2 vs. H3N2, the potential role of cross-reactivity in both domains warrants further immuno-epidemiological investigation.
Co-Author(s)
Samantha Kaweski, Immunization Programs and Vaccine Preventable Diseases Service, BC Centre for Disease Control, Vancouver BC;
Suzana Sabaiduc, Public Health Laboratory, BC Centre for Disease Control, Vancouver BC;
Lea Separovic, Immunization Programs and Vaccine Preventable Diseases Service, BC Centre for Disease Control, Vancouver BC;
Charlene Ranadheera, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg MB;
Nathalie Bastien, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg MB;
Danuta M Skowronski, Immunization Programs and Vaccine Preventable Diseases Service, BC Centre for Disease Control, Vancouver BC, School of Population and Public Health, University of British Columbia, Vancouver BC
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health