Nanopatch-Targeted Skin Vaccination against West Nile Virus and Chikungunya Virus in Mice

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 6; no. 16; pp. 1776 - 1784
• Main Authors: Prow, Tarl W., Chen, Xianfeng, Prow, Natalie A., Fernando, Germain J. P., Tan, Cindy S. E., Raphael, Anthony P., Chang, David, Ruutu, Merja P., Jenkins, Derek W. K., Pyke, Alyssa, Crichton, Michael L., Raphaelli, Kristin, Goh, Lucas Y. H., Frazer, Ian H., Roberts, Michael S., Gardner, Joy, Khromykh, Alexander A., Suhrbier, Andreas, Hall, Roy A., Kendall, Mark A. F.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16.08.2010; WILEY‐VCH Verlag
• Subjects: Administration, Cutaneous; Alphavirus Infections - prevention & control; Animals; Antigen-Presenting Cells - immunology; Chikungunya Fever; Chikungunya virus; Chikungunya virus - immunology; immunology; medicine; Mice; Mice, Inbred BALB C; microstructures; Nanostructures - chemistry; transcutaneous; Vaccination - methods; vaccine delivery; Vaccines, DNA - administration & dosage; Viral Vaccines - administration & dosage; West Nile Fever - prevention & control; West Nile virus; West Nile virus - immunology; West Nile Virus Vaccines - administration & dosage; West Nile Virus Vaccines - genetics; West Nile Virus Vaccines - immunology
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.201000331

The ‘Nanopatch’ (NP) comprises arrays of densely packed projections with a defined geometry and distribution designed to physically target vaccines directly to thousands of epidermal and dermal antigen presenting cells (APCs). These miniaturized arrays are two orders of magnitude smaller than standard needles—which deliver most vaccines—and are also much smaller than current microneedle arrays. The NP is dry‐coated with antigen, adjuvant, and/or DNA payloads. After the NP was pressed onto mouse skin, a protein payload co‐localized with 91.4 ± 4.1 APC mm−2 (or 2925 in total) representing 52% of the delivery sites within the NP contact area, agreeing well with a probability‐based model used to guide the device design; it then substantially increases as the antigen diffuses in the skin to many more cells. APC co‐localizing with protein payloads rapidly disappears from the application area, suggesting APC migration. The NP also delivers DNA payloads leading to cutaneous expression of encoded proteins within 24 h. The efficiency of NP immunization is demonstrated using an inactivated whole chikungunya virus vaccine and a DNA‐delivered attenuated West Nile virus vaccine. The NP thus offers a needle‐free, versatile, highly effective vaccine delivery system that is potentially inexpensive and simple to use. A miniaturized microneedle patch for targeted cutaneous delivery of conventional and DNA vaccines using the West Nile and Chikungunya virus model systems is developed. Once the vaccine is delivered through the skin, the number of antigen‐presenting cells decreases dramatically over the next 3 days, resulting in successful vaccination and protection.