{'fraction_non_alphanumeric': 0.020603015075376884, 'fraction_numerical': 0.0035175879396984926, 'mean_word_length': 5.614617940199335, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination

Significance Vaccine kinetics, the timing of antigen and/or adjuvant delivery to lymphoid organs, have recently been shown to substantially influence immune responses to subunit vaccines, but strategies to control vaccine kinetics in a clinically translatable manner are still lacking. MNs are arrays of solid micron-sized projections that have been utilized in early clinical trials for vaccine delivery. Here, we investigated whether implantable MN skin patches could be used to control vaccine kinetics. We show that sustained intradermal release of an HIV subunit vaccine from MNs enhanced GC responses and significantly improved humoral immunity compared with traditional bolus injections. The findings of this study have strong translational relevance as MNs, such as described here, can provide rapid needle-free vaccine administration. 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.