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Paradigm Shift Intervention Monitoring
Guizhou H5 Similar to Kawaoka Reassortant
“We recognised that, in the long term certainly, the information is going to get out, and maybe even in the mid term. But if we can restrict it in the short term and motivate governments to start getting busy in terms of building up the flu-defence infrastructure, then we’ve succeeded at a certain level,” he said.
“If we can slow down the release of the specific information that would enable somebody to reconstruct this virus and do something nefarious, even for a while, then that was a good thing.”
The above comments reflect serious concerns regarding the expertise on the NSABB board, as well as the rationale driving their requests. The two delayed/censored/redacted papers at Nature and Science use two very different approaches to produce H5 viruses that are efficiently transmitted in a ferret model.
The transmission in one case was generated by introducing three natural changes in a clade 2.1 isolate from Indonesia, which was then passed ten times in ferret to select for two additional changes. The new H5N1 had five in two gene segments and maintained its lethality. The small number of initial changes strongly suggests that similar results can be obtained without any additional information because clade 2.1 sequences with receptor binding domain changes are public, including the recent Bali cluster which involved three fatal cases.
Moreover, the paper at Nature involves transmission of an H5 reassortant which was not lethal, and a prior publication on the creation of such a reassortant using a 2009 clade 188.8.131.52 isolate from Hanoi (A/Vietnam/HN31604/2009) on an H1N1pdm09 genetic background (A/California/04/2009) provides methods. Thus, the detail for the creation of the reassortants has already been published, and the requirement for additional changes in this natural isolate is far from clear.
Studies by others have indicated the H1N1pdm09 M gene was critical for the jump of H1N1pdm09 from swine to humans, and all 12 2011 H3N2v human cases have an H1N1pdm09 M gene. Moreover, all 2010 H3N2v human cases have a PB1 change E618D, which is in all H1N1pdm09 isolates implicating this change in human transmission also. The reassortant described in the Nature paper would have both of these changes, which may explain the human transmission.
Although the sequence of A/Vietnam/HN31604/2009 has not been made public, a WHO phylogenetic tree includes this isolate, as well as closely related human and poultry public sequences from 2008 ad 2009 isolates. The most closely related human sequence is A/Vietnam/HN31432M/2008, which was sequenced by the Kawaoka lab and described in a prior publication. This sequences has a number of changes which were in the 2012 fatal case from Guizhou, China, A/Guizhou/1/2012, which included S133L, A188E, and R238K, highly concerns of a similar natural reassortant .
Thus, the transmission of H5 via two distinct mechanisms involving a small number of natural changes, strongly suggests that a natural isolate is far more likely that an attack by a bioterrorist, and discussions should be directed toward additional transmission experiments to more precisely define requirements for efficient transmission, and an aggressive H5 immunization campaign should be initiated.
A well immunized population would offer protection against a transmissible H5N1, regardless of source.