Broad and effective protection against influenza achieved by viral vectored vaccines

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Seasonal influenza vaccines are widely used, requiring annual revaccination, but vaccine effectiveness has been low in recent years, especially in older adults who are more likely to experience severe or fatal disease. In the event of an influenza pandemic, a new vaccine will be required, but will not become available in significant quantities until several months after the pandemic starts. At the Jenner Institute at Oxford University we have been working on the development of novel influenza vaccines that will be effective against both seasonal and pandemic influenza viruses, including in older adults, and one of the vaccines is now in a phase II clinical trial. We are now preparing to test further improvements to the vaccine.The first version of the vaccine includes only internal antigens of the influenza virus and boosts T cell responses to them. Multiple studies have demonstrated protection against both seasonal and pandemic influenza in people who have high T cell responses to these antigens, and we have demonstrated that we can boost responses, including in older adults, by vaccination. We will now include a further antigen into the vaccines, to induce antibodies against neuraminidase, which is a protein found on the surface of the influenza virus and is less variable that haemagglutinin which is the major antigen in licensed vaccines.We will also test different routes of vaccine administration. Licensed influenza vaccines are given to adults by intramuscular injection, and are known to increase antibodies to influenza haemagglutinin in the blood. However the virus infects the respiratory tract, and it may be possible to improve protection by delivering the vaccines to the respiratory tract also. The new vaccines will be tested in pigs which have already been exposed to influenza virus, to mimic the effect of vaccinating humans. We will study the induction of immune responses to both the internal antigens and neuraminidase, as well as testing for differences in vaccine efficacy after intramuscular, upper respiratory tract or lower respiratory tract immunisation. Viral vectored influenza vaccines expressing internal antigens have been tested in humans and shown to be safe, and to significantly boost T cell responses. Adding a further antigen and changing the route of vaccine administration may prove highly beneficial in improving vaccine efficacy.