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

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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.

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by the National Institute of Health (1R03DE021667-01A1). HSG is a co-inventor of a microneedle coating technology, which has been licensed to a US company. The patent application is still pending in the US patent office. No collaboration or other financial contracts exist between HSG and the licensee. The official technology transfer and license is managed by Georgia Tech Research Corporation.

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Authors and Affiliations

  1. Department of Chemical Engineering, Texas Tech University, 6th and Canton, Mail Stop 3121, Lubbock, Texas, 79409-3121, USA

    Yunzhe Ma, Wenqian Tao & Harvinder S. Gill

  2. Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, 97006, USA

    Shelly J. Krebs, William F. Sutton & Nancy L. Haigwood

Authors
  1. Yunzhe Ma
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  2. Wenqian Tao
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  3. Shelly J. Krebs
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  4. William F. Sutton
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  5. Nancy L. Haigwood
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  6. Harvinder S. Gill
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Corresponding author

Correspondence to Harvinder S. Gill.

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Ma, Y., Tao, W., Krebs, S.J. et al. Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity. Pharm Res 31, 2393–2403 (2014). https://doi.org/10.1007/s11095-014-1335-1

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  • DOI: https://doi.org/10.1007/s11095-014-1335-1

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