Fergusson, J.R., et al. Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant. Cell Rep, 2025 Jul 22, 44(7):115938.

Fergusson, J.R., et al. Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant. Cell Rep, 2025 Jul 22, 44(7):115938. PMID: 40608517

• This study develops an ex vivo human lymph node slice model that preserves the tissue architecture and cellular composition, allowing detailed analysis of immune responses to vaccine adjuvants. 
• From the perspective of QS-21, the ex vivo lymph node slice model is important because it allows for detailed investigation of the cellular and molecular mechanisms by which QS-21 enhances immune responses. The study demonstrates that QS-21 activates key innate immune cells, including monocytes and macrophages, which can promote dendritic cell maturation and T cell priming, as well as stimulate cytokine production from stromal and innate lymphoid cells. Understanding these interactions is crucial for optimizing QS-21-containing vaccines, as it sheds light on how the adjuvant modulates the tissue microenvironment to potentiate adaptive immunity. Additionally, the model offers a platform to evaluate donor-specific responses and individual variability, ultimately guiding the rational design of more effective adjuvant formulations and personalized immunization strategies involving QS-21. 
• The key findings regarding QS-21 adjuvant from the study are as follows: A) QS-21 activates resident macrophages and lymph node-resident macrophages, which are crucial for its adjuvant activity. This activation involves upregulation of cytokines and chemokines that promote immune cell recruitment and activation. B) It induces an early pro-inflammatory milieu characterized by cytokines such as IL-22, which is produced mainly by activated ILC3s in the lymph node microenvironment. This cytokine environment supports B cell responses and humoral immunity. C) QS-21 stimulates stromal cells to produce cytokines like TSLP and IL-33, which contribute to dendritic cell activation and T cell responses, emphasizing its capability to modulate multiple components of the lymph node microenvironment. D) It induces innate immune pathways that overlap with other adjuvants but also engages distinct mechanisms, suggesting unique modulation of immune responses. E) Variability in response to QS-21 among donors underscores the importance of individual immune backgrounds in shaping adjuvant efficacy, highlighting the value of ex vivo tissue models for personalized vaccine evaluation.
• These findings support the role of QS-21 in orchestrating a multifaceted innate immune activation that underpins its potent adjuvant properties, especially through interactions with macrophages, stromal cells, and innate lymphoid cells within the lymph node. The model highlights the dynamic interplay between resident immune cells and stromal components in initiating and shaping immune responses, providing a valuable platform for studying vaccine mechanisms and personalized immunotherapy strategies. 

Click here to access the full scientific paper.