An atlas of Influenza Hemagglutinin proteins; expression, characterisation and immunogenicity

The avian influenza situation in SE Asia and the possibility of a new pandemic has been of great concern for the general public and has received vocal coverage in the press. Both applicants were active in responding to media queries during the recent furore and take an proactive role in relating the scientific facts to the public at large in as simple a manner as possible. This will continue during the course of this award in addition to the normal dissemination of data via publication in learned journals.

Human influenza strains derive from zoonotic events in 1918, 1957 and 1968. The latter two pandemics (Asian and Hong Kong) were almost certainly caused by re-assortment amongst viral genomes of human and avian influenza isolates, possibly in an intermediate host but the 1918 influenza (Spanish influenza) appears to have been by direct adaptation of an avian strain to growth in human cells. In all these cases the principal, though not sole, component of change is the haemagglutinin (HA), the major surface glycoprotein of the virus. Further zoonoses are inevitable and the current extensive distribution of H5N1 avian influenza in SE Asia has been taken by many to signal that a zoonotic event is imminent. The threat is real and is not restricted to the H5 subtype; other avian influenza strains (H7 and H9) have shown occasional human infection and are also of epidemic concern. This heightened concern has resurrected difficult questions about policy in the face of a new pandemic and of what can be done to have in place a range of counter-influenza measures in the event they are needed. Chief among these concerns is ?what governs if and when such strains will emerge as human pathogens and what can research offer to counter the threat and/or increase preparedness??

In this application we seek to generate, characterise and use a bank of HA proteins representing the entire current range of human and avian subtypes. Importantly for this application, the HAs will be expressed and characterised in a common background and in a set of common formats so that direct side-by-side comparisons can be made. The HA bank will be used to characterise receptor usage, undoubtedly one of the main factors in tropism, and also to investigate immunogenicity, a limiting factor in the development of safe influenza vaccines. As a result of extensive preparatory work, the programme will deliver all its goals within the time frame of the award and, in so doing, contribute knowledge and a definite and valuable resource to the field.