Every year, scientists rush to create a vaccine for the newest strain of the influenza virus affecting the population. Current flu vaccines do not provide immunity against multiple strains of the flu, which is highly problematic due to the rapid rate of mutation and reassortment of genes in the virus that lead to new subtypes and varied protein expression (1).
A new use for the immunosuppressant drug rapamycin has researchers discussing the possibility of a new “universal” flu vaccine. Maureen McGargill’s team from St. Jude Children’s Research Hospital in Memphis found that, by treating mice with rapamycin before vaccinating them for the H3N2 virus, levels of CD8 T cells, which are memory cells that serve to attack infected cells and foreign molecules, against influenza increased. In addition, B cells, which produce antibodies that attack specific infected cells, could no longer class switch, or change production of antibody type. Upon injecting these mice with the influenza virus subtypes H5N1, H7N9, and H1N1, the team found that this combination of drug and vaccination had made the mice immune to other virus strains (1).
While the group originally believed that the improved creation of cytotoxic memory cells was responsible for the drug’s effectiveness in combatting the flu, they soon found that the drug’s interaction with B cells enhanced immunity (2). Apparently, rapamycin inhibits mTOR, a kinase protein involved in the activation of B cell class switching. This class switching causes B cells to change the type of antibody they produce, leading to the production of a variety of class-switched antibodies that targets and protects against subsequent infection with the same virus with high specificity. Class switching also decreases the production of antibodies that would attack conserved antigens. When rapamycin is applied, this new assortment of antibodies, while less specific to the original virus, could actually confer cross-strain immunity (1).
Rapamycin prevents class switching by disturbing the formation of germinal centers, which are areas in the body where B cells mature, mutate, and class switch. Treatment with rapamycin caused a decrease in germinal center formation in mice. The group believes that rapamycin also prevents B cells from migrating to these germinal centers. This blocks class switching even further, and hinders the survival of B cells that do mutate in germinal centers (1).
Scientists can apply this mechanism of providing immunity to other viruses, and some researchers may look into this class switching mechanism to help fight the human immunodeficiency virus (HIV). Immunologists have struggled with the ability to create vaccines that cover a wide range of antigens for decades, so, while further research and clarification is required, McGargill’s results may prove very valuable in the near future (1).
1. R. Keating et al., The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat. Immunol., 2013, doi:10.1038/ni.2741
2. J. Cohen. Immune Suppressant Unexpectedly Boosts Flu Vaccine. Science. 342, 413 (2013).