Reply to “Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited”

Lipsitch, Marc; Inglesby, Thomas V.

(i) These claims run counter to the original rationale for ferretgain-of-transmission studies. That rationale was to predict pandemic potential of natural isolates, which Fouchier earlier argued was associated with "airborne transmission" best studied in mammalian nonhuman hosts (24) . Likewise, Yoshihiro Kawaoka described the purpose of his ferret gain-of-transmission studies as "[t]o determine whether H5N1 viruses could be transmitted between humans" (25) , and the original reports of ferret transmission experiments say that pandemic potential is associated with the changes observed. For example: "Whether this virus may acquire the ability to be transmitted via aerosols or respiratory droplets among mammals, including humans, to trigger a future pandemic is a key question for pandemic preparedness . . . Identification of the minimal requirements for virus transmission between mammals may have prognostic and diagnostic value for improving pandemic preparedness" (17) . Similarly, in another ferret transmission study on synthetic 1918-like viruses from the Kawaoka lab, mutations conferring ferret transmissibility are specifically called "human-adaptive mutations" (26) . The CDC considers ferret transmissibility and human alpha-2,6 receptor binding to be 2 of the top 3 predictors of the threat of emergence of influenza viruses (27) . A recent publication by CDC influenza virologists suggests that they interpret specific mutations found in the ferret gain-of-transmission studies as signaling human adaptation, not specifically ferret adaptation (28) .