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Nature Science and Virology H5N1 Studies
The above comments confirm similarities between the H5N1 transmission studies described in the delayed paper at Nature with the delayed paper at Science and the CDC paper published at the journal Virology. These similarities add to the evidence that the current position of the NSABB is little more than a publicity stunt.
The NSABB initially recommended that the papers at Nature and Science be redacted because they provided recipes for a transmitting H5N1 which could be used for nefarious groups. However, transmitting H5N1 has never been a good choice because it can’t be controlled once released and the NSABB recommendation was made after the CDC paper was published in Virology and could be accessed by anyone who could double click on a link.
The CDC paper was published in November, 2011 and described transmission of a clade 2.2 H5N1 (A/egret/Egypt/1162/2006) after three receptor binding domain changes were introduced. Two of the changes, Q226L and G228S, have been investigated for years since they were both present in 1957 and 1968 pandemics, although neither has been reported in natural H5N1. The CDC added Q196R because of increased affinity for mammalian gal 2,6 receptors whne added to the above two changes. This modified H5 was placed on a clade 1 background (A/Vietnam/1203/2004) from an isolate that grew well in ferrets, due in part to PB1 E627K, and the CDC also used an N2 from seasonal H3N2 (A/Brisbane/10/2007). This construct transmitted via aerosol in a ferret model, as reported in the published and non-redacted paper in Virology.
The delayed Science paper by Ron Fouchier uses a different H5 (clade 2.1 from Indonesia), but uses three of the four changes in the CDC study (H5 Q226L / G228S with PB2 E627K). That construct is then passaged in ferrets ten times to produce a transmitting H5N1 that has acquired two additional changes. Fouchier comments indicate one of the two is Q196R, since he noted that a published study had 4 of the 5 changes, strongly suggesting that he was referring the CDC’s paper in Virology.
The above recent comments indicate similar changes were introduced into a clade 2.3 (from Vietnam) in the Yoshi Kawaoka paper delayed by Nature. That paper places the modified H5 on an H1N1pdm09 genetic background, removing the requirement for PB2 E627K. Thus, the Nature paper almost certainly reported the use of Q226L and G228S and either added or acquired Q196R.
Thus, although all three studies generated H5N1 transmission in ferrets using three different approaches, all used the same small number of receptor binding domain changes on H5 three different sub-clades (clade 2.1, 2.2, and 2.3) which are responsible for all human cases outside of southeast Asia (where clade 1 continues to cause human cases).
The delayed papers were distributed at the WHO meeting in Geneva, which was also attended by the acting chair of the NSABB, so all members should now realize that the recipe for all three studies are public, and the current NSABB meeting is little more than a publicity stunt that is hazardous to the world’s health.