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Paradigm Shift Intervention Monitoring
The CDC released a series of 35
H1N1 HA sequences at GISAID which were largely from 2011 isolates in
the United States. Included were three US sequences
(A/Pennsylvania/04/2011, A/Texas/08/2011, A/New Jersey/05/2011) which
were collected in March and were closely related to the Chihuahua
sub-clade sequences from Mexico. The three US sequences were
identical to each other, as well as three sequences released earlier
(A/Maryland/04/2011, A/Oregon/03/2011, A/Texas/07/2011) providing
further evidence for the spread of this sub-clade in the United
States. Two other closely related US sequences (A/Utah/08/2011
and A/Pennsylvania/02/2011) represent the eight US sequences which are
closely related to the sequences from Mexico
including the presence of K149N.
Two of the sequences from severe or fatal cases in Mexico have D225N, raising concerns that the US patients also have D225N, which is not found in the viral isolates from their samples due to collection or isolation issues.
The sequences from Mexico were generated by direct sequencing of the clinical samples, while the US sequences come from virus isolated in culture. Unreleased sequences from Mexico, as well as other countries in North and South America have D225N on a Chihuahua sub-clade genetic background, raising concerns that this receptor binding domain change is widespread and in samples represented by the CDC sequences.
This emerging sub-clade with D225N has led to a pandemic alert, and recent comments from the Air Force as well as sequences from vaccinated Air Force dependents has raised concerns that massive vaccination campaigns will have limited success.
The time for a new H1N1 vaccine targeting the Chihuahua sub-clade is long overdue.