Influenza viruses are important pathogens which pose an ongoing threat to public health due to their ability to mutate and evade immunity elicited by prior infection or vaccination. Their evolutionary diversity is facilitated by the plasticity of the antigenically variable head domain of the major surface glycoprotein, hemagglutinin (HA), which tolerates the accumulation of extensive mutations. To date, vaccines have focused on eliciting largely strain-specific immune responses toward the HA head. However, novel universal influenza vaccines aim to refocus immunity toward the immunosubdominant but conserved influenza virus HA stalk domain. Such vaccines could provide heterologous protection against diverse influenza viruses.
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