Evaluation of heterosubtypic immune responses in older people following seasonal or pandemic influenza vaccination

We are looking at testing influenza pandemic vaccines among healthy young and older people to improve protection against a possible influenza pandemic.
The spread of avian influenza H5N1 (bird flu) around the world has raised the real possibility of another influenza pandemic. Our unit has conducted evaluation of several vaccine candidates against H5 and H9 avian influenza in younger adults. Our studies, along with others, have found that it is usually necessary to give at least two doses of vaccine in order to produce effective protection.
However when vaccines against avian influenza have been tested in older people it seems that some individuals react much better than expected and get good responses even after one dose of vaccine.
We are planning to look at the immune systems of elderly people before and after being given avian influenza vaccines to see if we can find out why some people respond better. This might allow us to develop better vaccines that protect against different influenza strains

Influenza A is a respiratory infection of global importance and is responsible for frequent annual epidemics and infrequent pandemics. The emerging pan-epizoonotic of influenza A H5N1 in wild birds and poultry has been associated with over 250 human infections in several countries raising the fear that the next pandemic is imminent. Vaccination is the principal means of combating epidemic and pandemic influenza. In clinical trials among immunologically na?ve adults, at least two doses of conventional avian influenza H5 or H9 subunit vaccine are needed to induce moderate homologous antibody responses. Recent studies including older subjects have unexpectedly found that some people aged over 65 years have pre-vaccination neutralising antibodies to influenza H5 and H9 haemagglutinin. These subjects mount a robust antibody response to a single dose of H5 or H9 pandemic vaccine more consistent with responses seen following seasonal influenza vaccine suggesting that their immune systems are primed to at least some strains of avian influenza. Our clinical unit in Leicester has pioneered immmunogenicity assessment of avian influenza vaccines. Our aims, in collaboration with expert partners, Dr Jacqueline Katz (Centers for Disease Control) and Dr Del Giudice (Novartis Diagnostics), are to examine neutralising antibody responses to a range of human and non-human influenza viruses before and after seasonal and pandemic vaccination, identify haemagglutinin epitopes to which neutralising antibodies are directed, and evaluate cellular immune responses before and after pandemic H5 vaccination. Understanding of the basis of heterosubtypic neutralising antibody responses in humans may help steer the development of vaccines that induce broader immunity.