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Rapid Evolution of Vaccine Resistant H5N1 in Cairo Egypt
Recombinomics Commentary 20:57
November 09, 2008

HA sequences from last season’s Egyptian cases were recently released at Genbank by NAMRU-3.  Most of the sequences were related to isolates from the 2007/2008 season, including two isolates with the 3 BP deletion (Egypt/2289-NAMRU-3/2008 and Egypt/2546-NARMRU-3/2008), as well as four isolates related to the milder cases in southern Egypt (Egypt/10211-NAMRU3/2007, Egypt/1980-NAMRU3/2008, Egypt/2514-NAMRU3/2008, Egypt/3158-NAMRU3/2008).

One of the cases, however, was related to the vaccine-resistant strain that began to emerge in late 2007 in vaccinated flocks.  The vaccine resistant strain had a large number of non-synonymous changes, raising concerns that the resistance was being driven by poorly matched vaccines.  These changes were first reported by the National Veterinary Labs (NLQP), followed by a similar sequence in Israel, and sequences by the Capua lab and NAMRU-3 (see list below).

The fatal case (30F) in Cairo (Egypt/3300-NAMRU3/2008), had the changes seen in the vaccine resistant poultry isolates, as well as a large number of additional non-synonymous changes, raising concerns of rapid evolution away from the vaccine targets.  Included in the additional changes in the human case were S133L (position 133 is deleted in the isolates with the 3 BP deletion), D159N and A161T which create a new glycosylation site at position 159, L194I (between receptor binding positions 190 and 196), Q196K (Q196R is receptor binding domain change in Iraqi cluster), and A242T which creates a glycosylation site at position 240 (all of the above positions use H3 numbering).

The dramatic increase in non-synonymous changes, overlaid onto the changes reported earlier in poultry isolates, raises concerns of accelerated H5N1 evolution in Egypt, which may be linked to the vaccine program.

More information on sequences of recent poultry isolates would be useful.

Vaccine resistant isolates

National Veterinary Labs

Israel Veterinary lab

Capua lab


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