Why doesn’t the flu vaccine work?

You always hear that the flu vaccine isn’t 100% effective against seasonal influenza. We are studying people in the Rochester area who present with acute influenza infections. We collect, sequence, and isolate the viruses they are infected with, looking for changes in their antigenicity compared to the vaccine strains for that year. In parallel, we collect their serum at illness presentation and several time points afterwards, including when they have fully recovered. The serum is analyzed for its ability to react with both the vaccine strain and the strain the person was infected with. In this way we seek to understand if the failure to be protected from infection is due to variation in the viruses that are circulating compared to the vaccine strain, a failure to respond well to the vaccine, or a combination of both factors.  In addition, we are studying how infection modifies the memory B cell and serum antibody repertoire, and how prior immunity might affect these responses.