Current challenges: from the path of "original antigenic sin" towards the development of universal flu vaccines

Annual flu led by influenza viruses is contemplated to be one of the foremost global health challenges due to its rapid spread leading to the life-threatening epidemic or pandemic. An enormous number of people die due to flu and its associated intricacies every year. Annual vaccination is considered to be the gold standard strategy to protect the individual from acquiring infection and further decimation, although recent estimates suggest that overall flu vaccine effectiveness was within 19% to 53% in last five years. A significant weakness of current vaccination is its inability to protect an individual from different or mutant flu strain. Host immune system performs a vital role during natural infection or after vaccination leading to influenza-specific immunities. Previous imprints of common flu or vaccination may alter the outcomes of the current vaccination. Current flu vaccine regime does not consider the host immune status before vaccination. Irrespective of the previous influenza exposure history or prior flu vaccination, individual get flu vaccination based on WHO recommendation with selected strains which may be the reason why induction of broad immunities does not transpire with their testimonial. Over the last few decades, scientific research had identified the role of preexisting immunities on vaccination or natural infection outcome. In this review, we are proposing the concept of personalized flu vaccines depending on individual immune status. We will also discuss why individual was unable to induce broader immunities to protect itself from diverse influenza viruses and how we can accomplish that goal with the current findings.