Studying adjuvants in humans is challenging, generally relying on either expensive clinical trials or simplistic 2D cell culture models. Here we present a new 3D model using live human lymph node tissue to dissect the mechanism of action of the highly effective adjuvant LMQ.

Immune responses to vaccines are initiated in draining lymph nodes, with lymph nodes being highly structurally organised for effective immune cell interactions. By developing precision cut slices of healthy human lymph nodes, we can retain cell architecture over short-term culture enabling cell responses to LMQ to be studied in their native configuration ex vivo. This revealed a cascade of signalling from monocytes and macrophages, via IFNg produced by NK cells, to B cells responsible for protective responses. Type 3 innate lymphoid cells (ILC), a major population in the lymph node, were also indirectly activated by LMQ treatment to produce IL-22. Interestingly, LMQ also had a strong effect on resident stromal and endothelial cells, particularly inducing the production of chemokines involved in neutrophil recruitment, demonstrating their vital role in orchestrating and amplifying vaccine immune responses.

This study illustrates the use of precision-cut lymph node slices to reveal novel human biology, such as pathways involved in adjuvant-mediated immune activation.

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