Nanoparticles Mimic Particles Released by Mast Cells

Inspired by mast cells, researchers at Duke University have developed nanoparticles that act as lymph-node targeting vaccine adjuvants capable of boosting antibody and cell-mediated immune responses in mice. An adjuvant is a pharmacological or immunological agent that acts on other agents, such as a vaccine heightening an immune response. The team has previously shown that particles released by mast cells mediate inflammation, heighten immune response in lymph nodes, and support production of antibodies.

The team found that nanoparticless loaded with tumor necrosis factor resulted in increased production of antigen-specific antibodies when injected alongside a flu antigen. Nanoparticles loaded with IL-12 injected alongside antigen ovalbumin resulted in a significant increase in lymph node T-cells producing IFN-y.
The team's research demonstrates that their nanoparticles, loaded with different cytokines depending on the vaccine candidate, successfully modulates the immune response in the appropriate direction. Indeed, the nanoparticles replicate the structure, biochemical attributes, and functional capabilities of mast cell granules.
Mast cells are effective because the granules they release are transported to lymph nodes, where they influence immune response, without being diluted or degraded. The nanoparticles created by the researchers are the first man-made adjuvant to mimic this process, which makes them a much more effective adjuvant than previous vaccine methods.

Natural mast cell particles are rich in carbohydrates--specifically heparin--and proteases, so the researchers designed particles containing heparin with a carbohydrate chitosan shell, which provokes an immune response. The particles were confirmed to effectively bind tumor necrosis factor, which the particles then slowly released. Fluorescence labelled particles injected into mice were observed in the lymph nodes in minutes, and were observed in "striking quantities" in 45 minutes. The fluorescent particles were observed to be taken up in macrophages and dendritic cells within the lymph nodes. Injection with a low dose of antigen stimulated formation of lymph node germinal centers, while injection with antigen alone did not. Germinal centers signify lymph node swelling and remodeling in response to infection, and "contain activated B cells, as well as some dendritic cells and T cells, and are highly consequential to the development of adaptive immune responses and to the production of high-affinity antibodies of multiple subclasses."

The researchers also tested to show that particulate TNF was effectively expressed adjuvant activity, while soluble TNF did not when they were injected alongside a flu antigen. This adjuvant system was proved effective when the researchers injected mice with lethal doses of flu. The group that had been vaccinated with particulate TNF prior to recieving the flu had significantly higher survival rates. The researchers also showed that nanoparticles loaded with IL-12 stimulated production of IFN-y by T cells in the lymph nodes, demonstrating that the nanoparticles could be loaded with different cytokines to address specific issues. This cytokine loading need not conform to the template followed by mast cell granules.

This article is interesting because it attests to the ability of researchers to create products that mimic the natural system, and whose application may supplement the natural system. After learning to mimic the natural system, the product can be further tailored to address specific needs, unbounded by the template of the natural system. In addition, this particular development is also interesting as research in nanoparticles becomes more prevalent, and it may have potential to become an important form of adjuvant administration.
article: http://www.genengnews.com/gen-news-highlights/mast-cells-inspire-development-of-cytokine-loaded-nanoparticle-vaccine-adjuvants/81246251/