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

• Published in: Pharmaceutical research Vol. 31; no. 9; pp. 2393 - 2403
• Main Authors: Ma, Yunzhe, Tao, Wenqian, Krebs, Shelly J., Sutton, William F., Haigwood, Nancy L., Gill, Harvinder S.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2014; Springer Nature B.V
• Subjects: Administration, Oral; Animals; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Deoxyribonucleic acid; DNA; Drug Delivery Systems - instrumentation; Equipment Design; HIV - immunology; HIV Antigens - administration & dosage; HIV Antigens - immunology; HIV Infections - blood; HIV Infections - immunology; HIV Infections - prevention & control; Immune system; Immunity, Mucosal; Immunoglobulin A - analysis; Immunoglobulin A - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulins; Medical Law; Mouth - immunology; Needles; Ovalbumin - administration & dosage; Ovalbumin - immunology; Pharmacology/Toxicology; Pharmacy; Rabbits; Research Paper; Saliva - immunology; Vaccination - instrumentation; Vaccines; mucosal vaccination; oral cavity vaccination; lip vaccination; oral HIV; tongue vaccination
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1335-1

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. Figure ᅟ