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Nat Microbiol . Breadth of influenza A antibody cross-reactivity varies by virus isolation interval and subtype

tetano

Editor, Senior Moderator
Nat Microbiol


. 2025 Jun 10.
doi: 10.1038/s41564-025-02033-4. Online ahead of print. Breadth of influenza A antibody cross-reactivity varies by virus isolation interval and subtype

Bingyi Yang[SUP] 1 [/SUP], Katelyn M Gostic[SUP] 2 [/SUP], Dillon C Adam[SUP] 3 4 [/SUP], Ru Zhang[SUP] 3 [/SUP], Tal Einav[SUP] 5 6 [/SUP], Liping Peng[SUP] 3 [/SUP], Sook San Wong[SUP] 3 7 8 [/SUP], Tim K Tsang[SUP] 3 [/SUP], Derek A T Cummings[SUP] 9 10 [/SUP], Sheena G Sullivan[SUP] 11 12 [/SUP], Sarah Cobey[SUP] 2 [/SUP], Benjamin J Cowling[SUP] 3 4 [/SUP]



Affiliations
Abstract

Influenza virus infections generate antibodies that cross-react with antigenically similar viruses. However, the breadth of cross-reactivity is unclear. Here we analysed 200,000 haemagglutination inhibition (HAI) titrations from ferrets singly infected with A(H3N2) or A(H1N1)pdm09. We identified consistent influenza A virus subtype-specific patterns where breadth of HAI antibody cross-reactivity was associated with isolation time between tested and immunizing viruses. This was independent of virus strains, passage history and genetic mutations. A 6-year interval between virus isolation resulted in minimal HAI titres for A(H3N2), while A(H1N1)pdm09 demonstrated broader cross-reactivity with moderate titre reductions over the same interval. Analysis of HA substitutions revealed more amino acid substitutions between viruses for A(H3N2) and a greater reduction in HAI titres per substitution compared with A(H1N1). Longitudinal analysis of human antisera across age groups suggests that repeat A(H3N2) exposure increased HAI responses within the cross-reactivity range, with greater increases for more recent viruses. These results provide a framework for antigenically evolving pathogens such as influenza viruses.


 
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