DOI: 10.1002/adtp.202300102 ISSN:

Cavitation‐mediated Transcutaneous Delivery of Protein and Nucleotide‐based Antigen for Rapid High‐level Immune Responses

Johanna K Hettinga, Brian Lyons, Joel Balkaran, Pramila Rijal, Darcy Dunn‐Lawless, Lisa Caproni, Michael Gray, Kenneth S. Suslick, Constantin C Coussios, Robert C Carlisle
  • Pharmacology (medical)
  • Biochemistry (medical)
  • Genetics (clinical)
  • Pharmaceutical Science
  • Pharmacology
  • Medicine (miscellaneous)


Alternatives are needed to remove the pain, injury, cross‐infection and hazardous waste associated with needle and syringe (N+S)‐based vaccination. Reported here is the use of novel ultrasound‐responsive protein cavitation nuclei (pCaN), formed using the model antigen bovine serum albumin (BSA), to achieve effective transcutaneous delivery. Upon exposure to ultrasound, these pCaN instigate cavitation events which propel themselves and co‐located DNA vectors into the skin. Ultrasound parameters as well as pCaN and DNA concentration were refined to achieve optimal expression of encoded luciferase transgene. Twenty‐four hours post‐treatment, luciferase expression in the skin, by IVIS imaging, was 1.67 × 106 ±941943, photons/sec for N+S intradermal injection and 1.49 × 106 ±261832 for cavitation‐mediated delivery (p>0.05). Hence, there was no significant difference in luciferase level achieved, but improved homogeneity and reproducibility of expression was evident in mice treated using ultrasound‐mediated cavitation. Despite this equivalence in luciferase levels, a >5x higher level (p<0.02) of anti‐luciferase antibodies was achieved when cavitation was used versus N+S injection. Antibody levels against BSA, resulting from use of BSA pCaN, were equivalent for the two groups. PCaN can be formed from a range of antigenic protein and DNA can encode a range of antigenic proteins, so this approach has wide‐ranging implications for needle‐free vaccination.

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