Pre-existing heterosubtypic immunity provides a barrier to airborne transmission of influenza viruses

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. This protection from natural infection with H3N2 virus was independent of neutralizing antibodies. Pre-existing immunity with influenza B virus did not block H3N2 virus transmission, indicating that the protection was likely driven by the adaptive immune response. We demonstrate that pre-existing immunity can impact susceptibility to heterologous influenza virus strains, and implicate a novel correlate of protection that can limit the spread of respiratory pathogens through the air. Author summary Influenza viruses pose a major public health threat through both seasonal epidemics and sporadic pandemics. An individual's first influenza virus infection leaves long-lasting immunity, which plays an unknown role on susceptibility to airborne transmission of new viral strains. We show that pre-existing heterosubtypic immunity against the 2009 H1N1 pandemic virus protects recipient animals from airborne transmission of a seasonal H3N2 influenza virus, which is independent of cross-neutralizing antibodies. Pre-existing immunity with influenza B viruses was not protective suggesting that this phenomenon is driven by an adaptive response. Taken together, these data indicate that pre-existing immunity is an important barrier to airborne transmission and can influence the emergence and spread of potentially pandemic viruses.

Automated summary

Previous immunity can impact susceptibility to airborne transmission of heterologous influenza virus strains, providing protection that is independent of cross-neutralizing antibodies. This phenomenon is likely driven by adaptive immune responses, suggesting an important barrier to airborne transmission and potential influence on the emergence and spread of pandemic viruses.