Viruses are small infectious agents that can propagate in the living cells of humans, animals, plants, bacteria and fungi. They have extremely high genetic diversity and can cause emerging diseases in humans, animals and plants. To date, more than 200 human-infecting viruses have been reported, but currently approved antiviral counter-measures are available to treat only a few of them. One of the most common human-infecting respiratory viruses is the influenza virus, which can cause millions of infections and 250,000–640,000 deaths annually around the world. During the early stage of my academic career, I primarily studied the molecular mechanisms behind interspecies transmission of influenza viruses including the influenza A H1N1, H5N1 and H7N9 subtypes, in particular elucidating how changes in viral receptor binding affects the virus’s tropism and transmission. Influenza viruses can undergo antigenic shifts or drifts to quickly escape host immunity, leading to seasonal or pandemic influenza, which poses a great threat to public health. Since 1945, to achieve the goal of reducing the annual impact of influenza infection, the medical community has mainly used inactivated or subunit influenza vaccines for protection against infection in humans. However, their effectiveness largely relies on the accurate prediction of prevalent influenza virus strains by epidemiological surveillance. To solve this limitation, the scientific community is seeking a way to develop a universal influenza vaccine that can protect against highly mutated influenza viruses.
For decades, the academic and industrial fields have tried to develop a universal influenza vaccine based on the virus surface glycoprotein haemagglutinin, and little attention was paid to the other surface glycoprotein, neuraminidase (NA). The concept of influenza vaccine development took a significant turn with the publication of Krammer, Wilson and colleagues’ 2018 work in Cell on NA-reactive immunity in the human body during natural influenza virus infections. They showed that current influenza vaccines rarely induce NA-reactive B cells and, conversely, that influenza virus (the H1N1 or H3N2 subtype) infection induces both NA- and haemagglutinin-reactive B cells. More importantly, the NA-reactive antibodies displayed broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both the H1N1 and H3N2 subtypes. In addition, the NA-reactive antibodies conferred excellent prophylactic and therapeutic capacity against influenza virus infection in the mouse model. These results strongly suggest that influenza vaccines should be optimized to improve NA-reactive immune responses for durable and broad-spectrum protection against highly variable influenza virus strains.
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