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. 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.
Highlights
Airborne transmission is essential for the epidemiological success of human influenza A virus (IAV), which imposes a significant seasonal public health burden
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
During the 2017–2018 H3N2-predominant season, roughly 79,000 people died in the United States, which is greater than the number that died during the 2009 H1N1 pandemic [1,2,3]
Summary
Airborne transmission is essential for the epidemiological success of human influenza A virus (IAV), which imposes a significant seasonal public health burden. The impact of pre-existing immunity on the spread of influenza viruses has been understudied, and the few reports in this area have found that, surprisingly, pre-existing immunity against heterologous or homologous strains protects animals against subsequent influenza virus infections [10,11] In these studies, Steel et al demonstrated that pre-existing seasonal H1N1 or H3N2 immunity in recipient guinea pigs reduced transmission of the 2009 H1N1 pandemic virus [11] and Houser et al observed that pre-existing seasonal H3N2 immunity in donor ferrets prevented transmission of 2011 swine H3N2v virus [10]. Additional assessment of pre-existing immunity on susceptibility to infection is warranted
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