Cross-protection induced by influenza: from infection to vaccines

Influenza is one of the major respiratory diseases in humans and a large burden for human health and for the economy. Vaccination is the primary strategy to protect from influenza virus infection. Current influenza vaccines mainly induce strain-specific neutralizing antibodies, thereby providing protection against the virus strains present in the vaccine. However, influenza virus mutates frequently, generating new virus strains every year. Influenza vaccines have therefore to be updated annually to match these new strains. A vaccine or vaccination strategy capable of providing broad protection against a range of different influenza virus strains, so-called cross-protection, is urgently required. In this thesis we tried to understand the immune mechanisms contributing to cross-protection, to determine their respective role in protection against variant influenza virus strains, and to elucidate how these mechanisms could be induced or altered. We found that both antibody responses and T cell responses are required for optimal cross-protection. These cross- protecting immune responses could be simply induced by sequential immunization of mice with whole inactivated influenza virus vaccines derived from different virus strains. Cross-reactive influenza-specific antibody and T cell responses could also be elicited by immunization with reconstituted influenza virus membrane envelopes carrying an adjuvant and conserved influenza virus proteins. Our research paves a path for the development of new generations of cross-protective influenza vaccines