Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination
Author(s)Boopathy, Archana V; Mandal, Anasuya; Kulp, Daniel W.; Menis, Sergey; Bennett, Nitasha R; Watkins, Hannah C.; Wang, Wade; Martin, Jacob T; Thai, Nikki Tessa; He, Yanpu; Schief, William R.; Hammond, Paula T; Irvine, Darrell J; ... Show more Show less
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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 ∼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.
DepartmentMassachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Koch Institute for Integrative Cancer Research at MIT
Proceedings of the National Academy of Sciences
National Academy of Sciences
Boopathy, Archana V. et al. "Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination." Proceedings of the National Academy of Sciences 116, 33 (July 2019): 16473-16478.
Final published version