Influenza is a ubiquitous infection with a spectrum ranging from mild to severe. The mystery regarding such variability in the clinical spectrum has not been fully unravelled, although a role for the complex interplay among virus characteristics, host immune response and environmental factors has been suggested. Antivirals and current vaccines have a limited role in prophylaxis and treatment because they primarily target surface glycoproteins which undergo antigenic/genetic changes under host immune pressure. Targeting conserved internal proteins could lead the way to a universal vaccine which can be used against various types/subtypes. However, this is on the distant horizon, so in the meantime, developing improved vaccines should be given high priority. In this review, we discuss where the current influenza research stands in terms of vaccines, adjuvants, and how we can better predict the vaccine strains for upcoming influenza seasons by understanding complex phenomena which drive the continuous antigenic evolution.
Keywords: Influenza; adaptive immune response; adjuvants; antigenic evolution; antigenic sites; heterosubtypic immunity; influenza proteins; innate immune response; universal vaccine; vaccine mismatch.