Abstract
It has been almost a decade since the 2009 influenza A virus pandemic hit the globe causing significant morbidity and mortality. Nonetheless, annual influenza vaccination, which elicits antibodies mainly against the head region of influenza hemagglutinin (HA), remains as the mainstay to combat and reduce symptoms of influenza infection. Influenza HA is highly antigenically variable, thus limiting vaccine efficacy. In addition, the variable HA head occupies the upper strata of the immunodominance hierarchy, thereby clouding the antibody response toward subdominant epitopes, which are usually conserved across different influenza strains. Isolation of monoclonal antibodies from individuals recognizing such epitopes has facilitated the development of recombinant vaccines that focus the adaptive immune response toward conserved, protective targets. Here, we review some significant leaps in recombinant vaccine development, which could possibly help to overcome B cell and antibody immunodominance and provide heterosubtypic immunity to influenza A virus.
Highlights
Influenza viruses belong to the family of Orthomyxoviridae and consists of A, B, C, and D types
This review focuses on possible strategies for developing universal influenza vaccines, mainly based on HA
HA stem is an excellent candidate for the development of universal vaccines, anti-HA stem titers in human correlates only with reduced viral shedding but do not predict the severity of influenza infection [56, 57]
Summary
Influenza viruses belong to the family of Orthomyxoviridae and consists of A, B, C, and D types. Types A and B are currently circulating among humans [1,2,3,4]. Annual vaccination remains as the mainstay to prevent influenza infection, but, according to Centers for Disease Control and Prevention, it is effective only in 20–70% of the population, depending on season [6]. The current seasonal flu vaccines are either trivalent or quadrivalent containing HA from circulating H1N1, H3N2, and B/Victoria lineage or both influenza B lineages [9]. The annual vaccination becomes ineffective during pandemic outbreaks, in which a new viral strain of zoonotic origin acquires the ability to replicate in humans [10, 11]
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