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Vaccine Driven H5N1 Evolution in Egypt?

Recombinomics Commentary 18:24
March 3, 2008

The National Veterinary labs recently released 18 H5N1 HA sequences.  Included were nine sequences collected in December, 2007 or January, 2008.  Five of the nine sequences were from birds that had been vaccinated.  The sequences from four of the five were closely related.  Two were from the Sharkia Governorate, A/chicken/07665S-NLQP/2007 and A/turkey/Egypt/07203-NLQP/2007.  A third isolate was from Qalyobia, A/chicken/Egypt/7201-NLQP/2007, while the fourth was in Qena in upper Egypt, A/chicken/Egypt/7202-NLQP/2007.

These isolates had a large number of non synonymous changes, including P78S, D101N, H114R, S127P, R144G, S145P, F148Y, R166K, N166H, A189E, and M230V.  This high number of protein changes raise concerns of accelerated H5N1 evolution due to vaccine escape.

Moreover, these changes were present in additional isolates collected from additional locations, including Kom-Hammada, Behera (A/chicken/Egypt/07701S-NLQP/2007), Mansura, Dakahlia (A/chicken/Egypt/088S-NLQP/2008), and Ghamr, Dakahlia (A/chicken/Egypt/86Q-NLQP/2008), indicating this sub-clade is widespread in Egypt.

However, a series of sequences released by NAMRU-3 also had large numbers of non-synonymous changes, which were distinct from the list above.  These changes were also found in a large number of recent isolates.

This dramatic increase in genetic diversity in H5N1 in Egypt raises concerns that H5N1 evolution is being driven by large numbers of H5N1 infected birds, coupled with escape from the vaccine(s) currently in use.  This added diversity will create problems for future vaccination programs.

This diversity may also be impacting the human cases.  Many of the above isolates samples were collected in mid December, 2007, when there were five confirmed cases in Egypt.  The sequences from these human cases have not been released.

The release of these earlier sequences, as well as the two cases confirmed in the past week would be useful.

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