Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 39, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2102595118|1of8
Keywords
microneedles; 3D printing; continuous liquid interface production; vaccine; transdermal delivery
Categories
Funding
- Defense Threat Reduction Agency [HDTRA1-13-1-0045]
- Carbon, Inc.
- Stanford University Innovative Medicines Accelerator
- Joseph M. DeSimone Start-up Funds at Stanford University
- National Nanotechnology Coordinated Infrastructure [ECCS-1542015]
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Faceted microneedles produced with CLIP 3D printing technology show improved surface coating of vaccine components, enhanced cargo retention in skin, immune cell activation, and humoral immune response, as well as eliciting T cell responses in animal models. This platform offers a promising approach for noninvasive, self-applicable vaccination.
Vaccination is an essential public health measure for infectious disease prevention. The exposure of the immune system to vaccine formulations with the appropriate kinetics is critical for inducing protective immunity. In this work, faceted microneedle arrays were designed and fabricated utilizing a three-dimensional (3D)-printing technique called continuous liquid interface production (CLIP). The faceted microneedle design resulted in increased surface area as compared with the smooth square pyramidal design, ultimately leading to enhanced surface coating of model vaccine components (ovalbumin and CpG). Utilizing fluorescent tags and live-animal imaging, we evaluated in vivo cargo retention and bioavailability in mice as a function of route of delivery. Compared with subcutaneous bolus injection of the soluble components, microneedle transdermal delivery not only resulted in enhanced cargo retention in the skin but also improved immune cell activation in the draining lymph nodes. Furthermore, the microneedle vaccine induced a potent humoral immune response, with higher total IgG (Immunoglobulin G) and a more balanced IgG1/IgG2a repertoire and achieved dose sparing. Furthermore, it elicited T cell responses as characterized by functional cytotoxic CD8* T cells and CD4* T cells secreting Th1 (T helper type 1)-cytokines. Taken together, CLIP 3D-printed microneedles coated with vaccine components provide a useful platform for a noninvasive, self-applicable vaccination.
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