Alerting the immune system's watchmen to improve vaccines

Some vaccines, like the flu shot, contain a dead or weakened version of the disease-causing pathogen. Other vaccines, like those for hepatitis b and meningitis, contain just a protein, or other molecule (an "antigen") unique to the microbe. When there is a whole pathogen, the innate immune system is strongly activated, which includes alerting cellular watchmen called the toll-like receptors (TLRs). Antigen-based vaccines do not cause as strong a response, but they produce fewer side effects. Thus, an adjuvant is usually added to antigen-based vaccines to boost their effectiveness. A common adjuvant is a TLR agonist, or activator. In nature, multiple TLR activators work together to effectively direct the immune system. Aaron Esser-Kahn and colleagues investigated whether they could probe this biological machinery and improve the efficacy of antigen-based vaccines.

The researchers suspected that how the TLR agonists were arranged in space could affect their activity. So, they synthesized probes that displayed three different TLR agonists with a defined spatial orientation. The researchers found that their triply-linked activator more effectively raised an immune response than simply mixing the three ingredients together. In addition, by deconstructing the three-way activator into their two component parts, the team studied which components are most important and which arms of the immune response they activate. Esser-Kahn notes that this information will help researchers design better vaccines.