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Full Fouchier Formula for H5N1 FerretTransmission
Recombinomics Commentary 09:00
March 3, 2012

Actually, though, it's the wild-type virus that's odd. In general, when you give ferrets most kinds of H5N1 in their noses, said Fouchier, "they don't get sick at all". The strain he used, collected in 2005 in Indonesia, is known for causing unusual brain-related disease when put in ferrets' noses. Perhaps the mutant has lost this: the ferrets who got it in their noses, either by breathing it in or because it was put there, just got flu.

The above comments, as well as additional remarks, indicate the H5N1 used in the Ron Fouchier ferret transmission studies was A/Indonesia/5/2005 from the first confirmed human cases in Indonesia and the WHO clade 2.1 vaccine target.  The use of this H5N1 in prior ferret studies was described in a Fouchier 2011 American Journal of Pathology paper, “Pathogenesis of Influenza A/H5N1 Virus Infection in Ferrets Differs between Intranasal and Intratracheal Routes of Inoculation”.  That paper described different pathologies linked to various inoculation routes of A/Indonesia/05/2005, which match the descriptions in the recent report.

Thus, the Fouchier clade 2.1 Indonesian H5N1 virus could kill ferrets and cause neurotropic effects, but the transmitting H5N1 did not kill ferrets.  These results are similar to another published paper, which used a 2006 clade 2.2 virus from Egypt.  That CDC paper gave detailed descriptions for the creation of an H5N1 that also transmits in ferrets.  Similarly, the Yoshi Kawaoka paper delayed at Nature uses an H5 from another H5N1 sub-clade (2.3) which was placed on an H1N1pdm09 genetic background (as described in a prior publication) to also transmit in ferrets.

Thus, the full recipe for two of the three transmission studies is now known, as is the general formula for the third study.  Fouchier took a 2005 clade 2.1 isolate, A/Indonesia/05/2005, added three (HA Q226L, G228S; PB2 E627K) of the four changes in the CDC paper, and passaged the H5N1 in ferrets 10 times.  The CDC took a 2006 clade 2.2 isolate, A/egret/Egypt/1162/2006, added three HA changes, Q196R, Q226L, G228S and placed it on a clade 1 genetic background, A/Vietnam/1203/2004, which had PB2 E627K, and added seasonal N2 gene from A/Brisbane/10/2004.  Kawaoka took a 2009 clade 2.3 isolate, A/Vietnam/HN31604/2009, placed it on an H1N1pdm09 background (A/California/04/2009) and probably added the same two HA changes used in the Fouchier and CDC papers (Q226L and G228S).

Recent comments by some of the NSABB board members clearly demonstrates a profound lack of understanding of the published data, which is why the papers should be published in full immediately, and the NSABB board should be replaced with scientists more familiar with the scientific literature on H5N1 transmission.

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