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

Nat Biomed Eng. 2024 Oct;8(10):1226-1242. doi: 10.1038/s41551-024-01209-3. Epub 2024 May 6.

Abstract

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.

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Dendritic Cells / immunology
  • Female
  • Lymph Nodes* / immunology
  • Mice
  • Mice, Inbred C57BL*
  • Silicon Dioxide / chemistry
  • Ultrasonography / methods
  • Vaccination* / methods

Substances

  • Cancer Vaccines
  • Silicon Dioxide