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Durable lymph-node expansion is associated with the efficacy of therapeutic vaccination

  • Alexander J. Najibi,
  • Ryan S. Lane,
  • Miguel C. Sobral,
  • Giovanni Bovone,
  • Shawn Kang,
  • Benjamin R. Freedman,
  • Joel Gutierrez Estupinan,
  • Alberto Elosegui-Artola,
  • Christina M. Tringides,
  • Maxence O. Dellacherie,
  • Katherine Williams,
  • Hamza Ijaz,
  • Sören Müller,
  • Shannon J. Turley,
  • David J. Mooney

摘要

Following immunization, lymph nodes dynamically expand and contract. The mechanical and cellular changes enabling the early-stage expansion of lymph nodes have been characterized, yet the durability of such responses and their implications for adaptive immunity and vaccine efficacy are unknown. Here, by leveraging high-frequency ultrasound imaging of the lymph nodes of mice, we report more potent and persistent lymph-node expansion for animals immunized with a mesoporous silica vaccine incorporating a model antigen than for animals given bolus immunization or standard vaccine formulations such as alum, and that durable and robust lymph-node expansion was associated with vaccine efficacy and adaptive immunity for 100 days post-vaccination in a mouse model of melanoma. Immunization altered the mechanical and extracellular-matrix properties of the lymph nodes, drove antigen-dependent proliferation of immune and stromal cells, and altered the transcriptional features of dendritic cells and inflammatory monocytes. Strategies that robustly maintain lymph-node expansion may result in enhanced vaccination outcomes.