The road to a more effective influenza vaccine: Up to date studies and future prospects

Influenza virus causes an acute respiratory infection in humans. Frequent point mutations in the influenza genome and occasional exchange of genetic segments between virus strains help the virus evade the pre-existing immunity, resulting in epidemics and pandemics. Although vaccination is the most effective intervention, mismatches between circulating viruses and vaccine strains reduce vaccine efficacy. Furthermore, current injectable vaccines induce IgG antibodies in serum (which limit progression of influenza symptoms) but not secretory IgA antibodies in the respiratory mucosa (which prevent virus infection efficiently). Therefore, numerous studies have attempted to improve influenza vaccines. The discovery of broadly neutralizing antibodies has progressed research into antigen design. Studies designed to improve vaccine efficacy by changing the vaccine administration route have also been conducted. A thorough understanding of the mechanisms underlying the action of various vaccines is essential if we are to develop a universal influenza vaccine. Therefore, evaluating the quality and quantity of antibodies induced by vaccines, which determine vaccine efficacy, is critical. However, at present vaccine evaluation relies on hemagglutination inhibition tests, which only measure the quantity of antibody produced. Antibody repertoires comprise a set of antibodies with specific genetic or molecular features that correspond to their functions. Genetically and functionally similar antibodies may be produced by multiple individuals exposed to an identical stimulus. Therefore, it may be possible to evaluate and compare multiple vaccine strategies in terms of the quality and quantity of an antibody response induced by a vaccine by examining antibody repertoires. Recent studies have used single cell expression and high-throughput immunoglobulin sequencing to provide a detailed picture of antibody responses. These novel methods may be critical for detailed characterization of antibody repertoires induced by various vaccination strategies.