Pandemic influenza vaccines: what they have taught us about B cell immunology

The emergence of avian influenza viruses stimulated pandemic concerns and efforts to develop protective vaccines. Studies of the immune responses to experimental vaccines for pandemic influenza have taught us lessons about human immunity to influenza in general that can be applied to seasonal, pandemic, and even universal vaccine responses. For example, the concepts of targeting the hemagglutinin stalk and elicitation of stalk reactive antibodies grew out of studies of the 2009 pandemic H1N1 vaccines. More recently, the phenomenon of imprinting, the influence of early life exposure to influenza modifying responses to the viruses or vaccines later in life, has been reinforced through the study of potential pandemic influenza virus vaccines such as H7N9. These studies have also revealed potential strategies to improve responses to novel influenza strains and produce more broadly cross-reactive B cell and antibody responses. These concepts are discussed in detail in this review.