Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity

Abstract

Purpose The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. Method Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner lower lip and dorsal surface of the tongue of rabbits. Histology was used to confirm microneedle insertion, and systemic and mucosal immune responses were characterized by measuring antigen-specific immunoglobulin G (IgG) in serum and immunoglobulin A (IgA) in saliva, respectively. Results Histological evaluation of tissues shows that coated microneedles can penetrate the lip and tongue to deliver coatings. Using ovalbumin as a model antigen it was found that the lip and the tongue are equally immunogenic sites for vaccination. Importantly, both sites also induced a significant (p < 0.05) secretory IgA in saliva compared to pre-immune saliva. Microneedle-based oral cavity vaccination was also compared to the intramuscular route using two HIV antigens, a virus-like particle and a DNA vaccine. Microneedle-based delivery to the oral cavity and the intramuscular route exhibited similar (p > 0.05) yet significant (p < 0.05) levels of antigen-specific IgG in serum. However, only the microneedle-based oral cavity vaccination group stimulated a significantly higher (p < 0.05) antigen-specific IgA response in saliva, but not intramuscular injection. Conclusion In conclusion, this study provides a novel method using microneedles to induce systemic IgG and secretory IgA in saliva, and could offer a versatile technique for oral mucosal vaccination.

Cutaneous vaccination with coated microneedles prevents development of airway allergy

“…MNs were manually bent to make them perpendicular to the base. MNs were coated by using a micro-precision dip coating machine assembled in house [22, 25]. The coating solution consisted of carboxymethyl cellulose (CMC) (1%, w/v) (low viscosity, USP grade, CarboMer, San Diego, CA, USA) as a viscosity enhancer, Lutrol F-68 NF (BASF, Mt.…”

“…This FITC-conjugated Ova was coated on MNs and stereomicrographs were obtained before and after insertion of the MNs into mouse skin using a stereomicroscope (Olympus SZX16, Olympus America Inc.). The delivery efficiency of MNs coated with FITC-conjugated Ova was determined as described previously using calibrated fluorescent spectroscopy [22, 26]. …”

“…MNs are micrometer-sized needles, which can deliver the drug or antigen/allergen into the skin by rupturing the stratum corneum (topmost layer of the skin) and they can activate the immune response effectively [15, 22]. They have been widely explored in the development of infectious diseases vaccines [15, 22, 23]. For the very first time, we demonstrate here their efficacy to deliver the allergen in to the skin for primary protection against allergy progression in mice.…”

Microprojection arrays to immunise at mucosal surfaces

“…This may be due to: the vaccine structure (split instead of full particle [shown to generate mucosal IgA responses [42]]); the low dose (37 ng) delivered; or the number/type of dendritic cells targeted. This will be examined in future studies, however, the recent publication of microneedle delivery to the lip or tongue of rabbits that resulted in a mucosal IgA response further supports this theory [9]. The study differed from the research presented here in both antigen (particulate/DNA/protein compared with split virion) and the dose delivered with the Ma et al study delivering approximately 1400-3300 times more antigen.…”

“…Recently, the feasibility of delivering vaccines to the oral mucosa using microneedles has been demonstrated, with Ma et al [9] showing that vaccine delivery into the lip or dorsal tongue surface of rabbits was able to induce both mucosal and systemic immune responses. A mucosal site that has been largely overlooked in developing new mucosal vaccine delivery technologies is the buccal mucosa; the inside lining of the cheek that forms part of the oral mucosa.…”