The Flu!! New Targeting Strategies

Every year, around this time, we all fear the flu. Everyone runs to get their vaccine and hopes for the best. Yet, inevitably, there is always that co-worker that comes down with the flu anyway, and then so does a number of other people, and then occasionally so do you. Okay, so maybe not everyone gets their vaccination, but even if you do you still sometimes might fall sick. Why is this? Well every year the season flu strain is different. More scientifically, influenza A H3N2 and H1N1 subtypes and influenza B Yamagata and Victoria lineages remain constantly evolving, dynamic threats to our health each year, on a global scale. This is not due to lack of vaccines and antiviral drugs, just lack of their ability to target that they are meant to. These strains of virus have evolved into genetically distinct lineages, and these lineages have continued to co-circulate for decades.

According to a recent article published in Science Translational Medicine, a group of researchers lead by Ninshao Xia from China sought to address the current limitations of influenza vaccines and antivirals. They summed up the limitations of current strategies simply: “Current vaccines struggle to induce sufficient levels of cross-reactive neutralizing antibodies, and vaccine strains frequently become mismatched from continuously evolving influenza variants. In addition, the effectiveness of existing antiviral drugs for the treatment of influenza infection is limited because of short treatment windows and emerging antiviral drug resistance. Thus, there is an unmet medical need to develop more effective universal prophylactic and therapeutic approaches against influenza infection.” This is exactly what this group set out to address.

Recently, what is known as ‘broadly neutralizing antibodies’ have emerged as a new strategy to address the issue of the elusive influenza. These are essentially antibodies that target antigens that are ever present, and are weak points for the virus. So while the virus may be ever changing, it maintains these antigens as part of itself regardless of how it might evolve, and exploiting these antigens therapeutically has the ability to cripple the disease. In the research from Dr. Xia’s group, they report the development of a chimeric monoclonal antibody which they call C12G66, that has the ability to cross neutralize viral strains spanning 76 years of influenza B by targeting hemagglutinin (HA). When tested in mice and ferrets, C12G6 was able to confer strong cross protection of these animals against various influenza B strains, and to a greater extent than any other vaccines tested. Further investigation revealed that this protection was due to C12G6 inhibiting the virus through multiple mechanisms. The others state that C12G6 could “prevent viral entry, egress, and HA-mediated membrane fusion and could trigger antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity responses.” In other words, it worked and it worked in multiple ways. To put it simply, C12G6 holds promise for the development of much more effective flu vaccine design and may lay the foundation for what could eventually be a “truly universal” flu vaccine.

Sources: Science Translational Medicine, Wikipedia, Pixabay, TedEd, Youtube