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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts 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
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