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Defining transmissible dose 50%, donor #inoculation dose that results in #airborne #transmission to 50% of contacts, for 2 #pandemic #influenza viruses in ferrets

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By G.M.

Abstract

Ferrets are widely used to model airborne transmission of influenza viruses in humans. Airborne transmission is evaluated by infecting donor ferrets with a high virus dose (106 infectious units) and monitoring transmission to contact animals sharing the same airspace. However, humans can be infected with a broad range of influenza virus doses. Therefore, we evaluated the relationship between virus inoculation dose and transmission for two pandemic influenza viruses in ferrets. Donor ferrets were inoculated with 100 to 106 tissue culture infectious dose 50 (TCID50) of the 2009 pandemic H1N1 or 1968 H3N2 pandemic virus, and were then paired with respiratory contacts. Using the proportion of donors that became infected across virus doses, we calculated the infectious dose 50 (ID50). Subsequently, by comparing the proportion of respiratory contacts that became infected, we calculated the transmissible dose 50% (TD50): the donor inoculation dose that resulted in transmission to 50% of contacts. For the 2009 H1N1 virus, the ID50 and TD50 were equivalent at <1 TCID50. However, for the 1968 H3N2 virus, the ID50 and TD50 were <4 and 103.49 TCID50, respectively. The increased TD50 for the H3N2 virus was associated with reductions in peak viral titers and viral shedding in donors over decreasing virus inoculation doses. Collectively, these studies define a new measure of transmission that permits comparisons of transmissibility over a log scale. Using this metric, we show the 1968 pandemic H3N2 virus has reduced transmissibility in ferrets relative to the 2009 pandemic H1N1 virus.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.04.641289v1

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