An ideal influenza vaccine: what does it look like and what components play a role in inducing cross-immune reactivity

Influenza is a very contagious disease that causes serious illness and death every year. Antigenic drifting and antigenic shifting of the virus leads to the emergence of new viral strains which can evade the human immune system and thus cause epidemics and pandemics. Vaccination is the primary strategy to protect the human population from infections with influenza viruses but the current vaccines do not provide sufficient protection against new strains. Predicting the next pandemic is impossible and therefore it is important to find new vaccines that can induce cross-immune reactivity. The innate immune system targets invading viruses first and activates the adaptive immune response which consists of a humoral and a cellular part. The humoral response can block viral infection with antibodies that can bind viral proteins and the cellular response leads to clearance of the virus with T-cells when a host has been infected. The hemagglutinin surface protein of the virus is currently used as a target for vaccination but because this protein changes rapidly vaccinating against hemagglutinin is ineffective in inducing cross-immune reactivity. The M2 surface proteins, the internal nucleoprotein and the hemagglutinin stem provide more promisin! g targets for vaccination when a broad immune response is required. The development of a universal influenza vaccine would lead to prevention of pandemic outbreaks. Of all the possible vaccines that are in use or in development DNA vaccines against the nucleoprotein, the M2 protein or the HA stem, possibly with the addition of an adjuvant, seem like an ideal candidate for a universal vaccine.