Najibi et al. showed that compared to liquid bolus and common depot-based formulations, a mesoporous silica (MSP) nanoparticle formulation of model antigen induced stronger, more persistent dLN volume expansion. This was associated with biomechanical LN remodeling and altered transcriptional activity of cDC2s and inflammatory monocytes, which mediated long-term antigen presentation and more potent, durable immune responses. In a therapeutic model of mouse melanoma, MPS antigen delivery safely induced longer-lasting antitumor efficacy and memory than bolus vaccination. LN expansion induced by antigen-free MPS delivery enhanced subsequent liquid bolus vaccine-induced antitumor efficacy.
Contributed by Paula Hochman
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.
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University,
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (2) Department of Cancer Immunology, Genentech, Inc., South San Francisco, CA, USA. (3) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (4) Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (5) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (6) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (7) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (8) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. Institute for Bioengineering of Catalonia, Barcelona, Spain. (9) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. Harvard Program in Biophysics, Harvard University, Cambridge, MA, USA. (10) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (11) Department of Cancer Immunology, Genentech, Inc., South San Francisco, CA, USA. (12) Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. (13) Department of Cancer Immunology, Genentech, Inc., South San Francisco, CA, USA. (14) Department of Cancer Immunology, Genentech, Inc., South San Francisco, CA, USA. (15) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. mooneyd@seas.harvard.edu. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. mooneyd@seas.harvard.edu.
