When the immune system encounters a disease-causing pathogen, it releases antibodies that can bind to specific regions of the bacterium or virus and help to clear the infection. These proteins are generated by B cells which, upon detecting the pathogen, can begin to mutate and alter the structure of the antibody they produce: the better the antibody is at binding to the pathogen, the more likely the B cell is to survive. This process of evolution produces B cells that make more effective antibodies. After the infection, some of these cells become ‘memory B cells’ which can be stimulated in to action when the pathogen invades again.
Many vaccines also depend on this process to trigger the production of memory B cells that can fight off a specific disease-causing agent. However, it is unclear to what extent memory B cells that already exist are able to continue to evolve and modify their antibodies. This is particularly important for the flu vaccine, as the virus that causes influenza rapidly mutates. To provide high levels of protection, the memory B cells formed following the vaccine may therefore need to evolve to make different antibodies that recognize mutated forms of the virus.
It is thought that the low effectiveness of the flu vaccine is partially because the response it triggers does not stimulate additional evolution of memory B cells. To test this theory, Hoehn et al. developed a computational method that can detect the evolution of B cells over time. The tool was applied to samples collected from the blood and lymph nodes (organ where immune cells reside) of people who recently received the flu vaccine. The results were then compared to B cells taken from people after different infections, vaccinations, and other conditions.
Hoehn et al. found the degree to which B cells evolve varies significantly between conditions. For example, B cells produced during chronic HIV infections frequently evolved over time, while such evolution was rarely observed during the autoimmune disease myasthenia gravis. The analysis also showed that memory B cells produced by the flu vaccine were able to evolve if recruited to the lymph nodes, but this was rarely detected in B cells in the blood.
These findings suggest the low efficacy of the flu vaccine is not due to a complete lack of B cell evolution, but likely due to other factors. For instance, it is possible the evolutionary process it stimulates is not as robust as in other conditions, or is less likely to produce long-lived B cells that release antibodies. More research is needed to explore these ideas and could lead to the development of more effective flu vaccines.