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Paradigm Shift Intervention Monitoring
HA Changes In
Case In Shenzhen Raise Concerns
In addition to receptor binding domain changes Q196K and S227R, it has T192I, which is also in the Shangxi clade 7 vaccine resistant sequence, A/chicken/Shangxi/2/2006, as well as Shantou H5N1 sequences. Similarly, Q196K is in the vaccine resistant H5N1 sub-clade in Egypt.
The HA cleavage site has added an R and matches H5N1 sequences in Vietnam, Hong Kong, Guangdong, Jiangxi, and Guangxi, including a 2009 case, A/Guangxi/01/2009 (see list here). Moreover, R327I at the beginning of the HA cleavage site is in recent duck sequences in Zhejiang as well as wild bird sequences from Hong Kong in 2009 (see list here).
The large number of HA changes strongly suggest the Shenzhen H5N1 sub-clade will also be vaccine resistant. Moreover, the matches with these prior H5N1 cases provide strong evidence for recombination and rapid evolutionary change.
The recent results on changes requiring airborne transmission raise concerns that H5N1 can acquire a similar set of polymorphisms (5 changes in 2 genes), and prior data on receptor binding domain changes in H5N1 involved in human clusters raise concerns about changes at positions 186, 196, 223, 227, and 230.
The Shenzhen has changes at 4 of those 5 positions. The second gene involved in efficient transmission is likely to be PB2 and the E627K change. Release of the PB2 sequence from the Shenzhen case would be useful.
The above changes in a human H5N1 case and an unknown source raise serious transmission issues (which can be enhanced by further recombination), and demand immediate release of the 5 changes linked to H5N1 airborne transmission.
HA changes (H3 numbering) include: