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

doi:10.1038/s41551-024-01209-3

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

Nat Biomed Eng. 2024 May 6. doi: 10.1038/s41551-024-01209-3. Online ahead of print.

Authors

Alexander J Najibi^{1

2}, Ryan S Lane³, Miguel C Sobral^{1

2}, Giovanni Bovone², Shawn Kang^{1

2}, Benjamin R Freedman^{1

2}, Joel Gutierrez Estupinan^{1

2}, Alberto Elosegui-Artola^{1

2

4}, Christina M Tringides^{1

2

5}, Maxence O Dellacherie^{1

2}, Katherine Williams³, Hamza Ijaz², Sören Müller³, Shannon J Turley³, David J Mooney^{6

7}

Affiliations

¹ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
² Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
³ Department of Cancer Immunology, Genentech, Inc., South San Francisco, CA, USA.
⁴ Institute for Bioengineering of Catalonia, Barcelona, Spain.
⁵ Harvard Program in Biophysics, Harvard University, Cambridge, MA, USA.
⁶ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. mooneyd@seas.harvard.edu.
⁷ Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. mooneyd@seas.harvard.edu.

PMID: 38710838
DOI: 10.1038/s41551-024-01209-3

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.

Abstract

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