Vaccination is the principal means of combating and controlling epidemic seasonal and pandemic influenza. Seasonal epidemic influenza viruses regularly change and adapt, so vaccines need to be regularly updated to account for this. As influenza vaccines induce antibody responses that are fairly shortlived, annual immunisation with regularly updated influenza vaccine is recommended for seasonal influenza, but would not be expected to protect against a pandemic event. A pandemic occurs when a completely new influenza virus appears so the seasonal vaccines will not protect against it. Avian influenza (bird flu) has recently spread around the world and affected several hundred people. The concern is that it could adapt to humans and become a new pandemic virus. H5, H9 and H7 bird flu viruses have infected people. In clinical trials among immunologically naive young adults, at least two doses of conventional avian influenza H5 or H9 subunit vaccine are needed to induce moderate antibody responses against the vaccine strain. However, studies including older subjects have unexpectedly found that >15% and >50% of people aged over 65 years have pre-vaccination antibodies to influenza H5 and H9 haemagglutinin (HA) respectively even though they have not been exposed to these viruses. In contrast to recipients of avian influenza vaccines who are antibody-negative at baseline, these people mount a robust antibody response to single dose H5 or H9 pandemic vaccine suggesting that they are effectively primed to at least some strains of avian influenza. It is important to have an understanding of the basis for this as it may help the development of vaccines that induce broader immunity to a range of influenza viruses. This would be important if new vaccines could induce a wider range of antibody responses than just to the vaccine strains. This proposal focuses on those subjects whose immune systems already exhibit antibodies to avian H5 with a goal of investigating the antibody and cellular basis of the immune response to seasonal and pandemic vaccination. We will examine neutralising antibody responses to a range of human and non-human influenza viruses before and after seasonal and pandemic vaccination and evaluate cellular B and T cell immune responses before and after pandemic H5 vaccination
