Editors' ChoiceNanomedicine

Nanoscale Mimics of Mast Cell Messengers

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Science Translational Medicine  28 Mar 2012:
Vol. 4, Issue 127, pp. 127ec53
DOI: 10.1126/scitranslmed.3004036

Vaccine adjuvants often exert their immunostimulatory effects at their injection sites, whereas natural infections raise immune responses locally and also in remote sites, such as the lymph nodes and the spleen. Some of the messengers that communicate information from the site of infection to lymph nodes are granules released near the infection by mast cells. Once safely lodged in the lymph nodes, these granules release cytokines that shape the immune response. Now, to produce vaccines that more faithfully mimic Mother Nature, St. John et al. have designed synthetic analogs of mast cell granules, demonstrating that they too can travel to lymph nodes and incite an immune response against pathogens.

St. John and co-workers designed nanoparticles between the sizes of 200 and 1000 nm consisting of heparin—a major constituent of natural mast cell granules—and chitosan. The positively charged chitosan was attracted to negatively charged heparin to form the particles. Cytokines were loaded into the particles and released slowly over the course of at least 24 hours. The authors used tumor necrosis factor (TNF) as the cytokine because it is found naturally in mast cell granules. TNF-loaded particles were tracked to the draining lymph nodes, where the release of TNF promoted lymph node remodeling, including germinal center formation. St. John et al. found that, when formulated with an influenza antigen, particulate-delivered TNF was an effective adjuvant that protected mice against a lethal flu challenge, to a similar degree as a traditional alum-adjuvanted vaccine. Interestingly, they could also shift the Th1/Th2 polarization of the immune response by including another cytokine, interleukin-12, in the particles.

Nanoparticule-based vaccines are becoming increasingly sought after. The success of these types of approaches may hinge on understanding exactly how such particles shape immunity, so that they can be best engineered as synthetic mimics in vaccines, not only for flu but for other diseases as well.

A. L. St. John et al., Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes. Nat. Mater. 11, 250–257 (2012). [Abstract]

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