Immunobiology of Influenza Vaccines

Vaccinationis the primary strategy for prevention and control of influenza. The surface hemagglutinin (HA) protein of the influenza virus contains two structural elements (head and stalk) that differ in their potential utility as vaccinetargets. The head of the HA protein is the primary target of antibodies that confer protective immunity to influenza viruses. The underlying health status, age, and gene polymorphismsof vaccinerecipients and, just as importantly, the extent of the antigenic match between the viruses in the vaccineand those that are circulating modulate influenza vaccineprotection. Vaccineadjuvants and live attenuated influenza vaccineimprove the breadth of immunity to seasonal and pandemic virus strains. Eliciting antibodies against the conserved HA stem region that cross-react with HAs within influenza virus types or subtypes would allow for the development of a universal influenza vaccine. The highly complex network of interactions generated after influenza infection and vaccinationcan be studied with the use of systems biology tools, such as DNA microarraychips. The use of systems vaccinology has allowed for the generation of gene expression signatures that represent key transcriptional differences between asymptomatic and symptomatic host responses to influenza infection. Additionally, the use of systems vaccinology tools have resulted in the identification of novel surrogate gene markers that are predictors of the magnitude of host responses to vaccines, which is critical to both vaccinedevelopment and public health. Identifying associations between variations in vaccineimmune responses and gene polymorphismsis critical in the development of universal influenza vaccines.