Public Release: 

Alerting the immune system's watchmen to improve vaccines

American Chemical Society

As the days get colder and shorter, we carve jack-o-lanterns and drink pumpkin spice lattes. But one fall tradition can actually keep you healthy: getting your flu shot. Like all vaccines, the flu shot trains the immune system to fend off infection, but some need help to produce the full effect. Today, in ACS Central Science, researchers report a new way to help improve vaccines using molecules that more effectively direct the immune system.

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.

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The authors acknowledge funding from UC Irvine, the Hellman Family Foundation, the National Institutes of Health and the National Science Foundation.

The paper will be freely available on Oct. 28 at this link: http://pubs.acs.org/doi/full/10.1021/acscentsci.5b00274

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