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H5N1 Clade 7 Spread to Vietnam
Recombinomics Commentary 14:17
August 28, 2008
Anh told VNA that the H5N1 strain was named "seven." The story did not mention a clade number. Typically, the story said, "strain one" of the H5N1 virus has infected birds in the Mekong delta, while strains two, three, and four have been found to infect birds in the country's Red River Basin.
Nguyen Van Cam, director of Vietnam's Central Animal Diagnosis Centre, told VNA the lab was doing more tests to better characterize the strain and that he expected results soon.
The above comments from a CIDRAP update describe a new H5N1 clade in Vietnam, which is likely clade 7. The first confirmed H5N1 in mainland China was A/Beijing/01/2003, which is a clade 7 isolate from a fatal case in Beijing in 2003, as seen in the WHO pandemic vaccine target phylogram. A more recent clade 7 isolate is from A/chicken/Shanxi/2/2006 which was involved a significant poultry outbreak in Shanxi in 2006. This outbreak was described in multiple OIE reports, which detailed the use of three different anti-sera in efforts to bring the outbreak under control. The public sequences include multiple non-synonymous changes clustered around receptor binding domain position 190 (H3 numbering), as well as additional acquisitions, which subsequently appeared in the clade 2.2 vaccine resistant strain in Egypt and Israel.
These shared polymorphisms which were reported on genetically distinct H5N1 backgrounds illustrate the movement of polymorphisms via homologous recombination. This type of rapid change can defeat efforts using mismatched vaccines.
It is of note that the poultry vaccine effort in Egypt, like the effort in Vietnam, includes use of an H5N2 vaccine directed against a low path H5 target, which has also been used in Hong Kong. The extended use of these poorly matched vaccines has been associated with the repeated re-emergence of H5N1 in vaccinated regions, which may also be associated with an accelerated evolution to escape from the mismatched vaccine.
This type of evolution associated with mismatched vaccines is not limited to H5N1. Last season the trivalent seasonal flu vaccine was mismatched in all three targets. The mismatch in H1N1 was less obvious because the Bribane/59 isolates were being characterized as Solomon Island/3-like, even though Solomon Island/3 was no longer in widespread circulation in 2007/2008. This season the H1N1 target is switching to Brisbane/59, but early HA sequences from South Africa already has a cluster of changes near the receptor binding domain position 190 including adjacent polymorphisms matching H1N1 sequences from the 1940’s.
These rapidly evolving sequences were on the common H1N1 sequences which included Tamiflu resistance marker, H274Y, which is now at 100% of H1N1 isolates in South Africa and Australia.
The season and pandemic vaccine mismatches, and associated influenza evolution, remain causes of concern.
Recombinomics Paper at Nature Precedings