Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 33, Pages 16473-16478Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1902179116
Keywords
microneedles; antibody response; vaccine delivery
Categories
Funding
- National Institute of Allergy and Infectious Diseases of the NIH [UM1AI100663, AI104715]
- Koch Institute from the National Cancer Institute, International AIDS Vaccine Initiative [P30-CA14051]
- Ragon Institute of Massachusetts General Hospital, MIT, and Harvard
- Vaxess Technologies, Inc.
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Sustained exposure of lymphoid tissues to vaccine antigens promotes humoral immunity, but traditional bolus immunizations lead to rapid antigen clearance. We describe a technology to tailor vaccine kinetics in a needle-free platform translatable to human immunization. Solid pyramidal microneedle (MN) arrays were fabricated with silk fibroin protein tips encapsulating a stabilized HIV envelope trimer immunogen and adjuvant, supported on a dissolving polymer base. Upon brief skin application, vaccine-loaded silk tips are implanted in the epidermis/upper dermis where they release vaccine over a time period determined by the crystallinity of the silk matrix. Following MN immunization in mice, Env trimer was released over 2 wk in the skin, correlating with increased germinal center (GC) B cell responses, a similar to 1,300-fold increase in serum IgG titers and a 16-fold increase in bone marrow (BM) plasma cells compared with bolus immunization. Thus, implantable MNs provide a practical means to substantially enhance humoral immunity to subunit vaccines.
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