Paradigm Shift Intervention Monitoring
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Commentary
Increasing
Low Reactors On Novel H1N1 Genetic Background
Recombinomics
Commentary 17:20
December 16, 2010
Earlier analysis of this new sub-clade demonstrated a significant reduction in titers of anti-sera directed against the new sequences when tested on California/7. These titer drops and vaccine escape highlighted the need for a new pH1N1 target. However, the recent sequences identify additional changes on this background that were in regions liked to immunological escape in seasonal H1N1, when H274Y was fixed. Those sequences had a number of changes flanking the receptor binding position 190. All had A193T, but these sequences also had one of more additional changes at positions 187, 189, and 196. Nine of the sequences had S188T, signaling a similar paradigm for immunological escape.
However these sequences also had changes at positions linked to low reactor status in H1N1 last season (five with G158E, three with N159K, two with D225G) and several isolates had two changes at the four positions, signaling immunological selection.
The appearance of D225G was of considerable concern because the change was also linked to severe and fatal cases. D225G was most common in eastern Europe (in Ukraine and Russia), but it was detected at a relatively low frequency. In contrast, another change at the same position, D225E, was not linked to more severe cases and was common in western Europe, including England, where levels approached 40% of sequences from isolates collected in late summer and early fall of 2009.
These high levels of D225E raised concerns that levels of D225G could increase to similar levels in an emerging variant, leading to a dramatic rise in severe and fatal cases, which would tax health care delivery.
Such increases are being reported in England, where the number of severe / ICU cases being reported at local hospitals are increasing daily. Shortages of ECMO machines are being reported, even though overall levels of H1N1 are low and the flu season is just beginning.
This spike in severe and fatal cases raise concerns that D225G or other receptor binding domain changes are on the rise, highlighting the need for prompt release of sequences from these UK cases.
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