Abstract Human-to-human transmission of influenza viruses is a serious public health threat, yet the precise role of immunity from previous infections on the susceptibility to airborne infection is still unknown. Using the ferret model, we examined the roles of exposure duration and heterosubtypic immunity on influenza transmission. We demonstrate that a 48 hour exposure is sufficient for efficient transmission of H1N1 and H3N2 viruses. To test pre-existing immunity, a gap of 8–12 weeks between primary and secondary infections was imposed to reduce innate responses and ensure robust infection of donor animals with heterosubtypic viruses. We found that pre-existing H3N2 immunity did not significantly block transmission of the 2009 H1N1pandemic (H1N1pdm09) virus to immune animals. Surprisingly, airborne transmission of seasonal H3N2 influenza strains was abrogated in recipient animals with H1N1pdm09 pre-existing immunity.



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Citation: Le Sage V, Jones JE, Kormuth KA, Fitzsimmons WJ, Nturibi E, Padovani GH, et al. (2021) Pre-existing heterosubtypic immunity provides a barrier to airborne transmission of influenza viruses. PLoS Pathog 17(2): e1009273. https://doi.org/10.1371/journal.ppat.1009273