Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization

Abstract

Intradermal immunization using microfabricated needles represents a potentially powerful technology, which can enhance immune responses and provide antigen sparing. Solid vaccine formulations, which can be coated onto microneedle patches suitable for simple administration, can also potentially offer improved shelf-life. However the approach is not fully compatible with many vaccine adjuvants including alum, the most common adjuvant used in the vaccine market globally. Here, we introduce a polyphosphazene immunoadjuvant as a biologically potent and synergistic constituent of microneedle-based intradermal immunization technology. Poly[di-(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine adjuvant and as a key microfabrication material. When used as part of an intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates superior activity in pigs compared to intramascular administration and significant antigen sparing potential. It also accelerates the microneedle fabrication process and reduces its dependence on the use of surfactants. In this way, PCPP-coated microneedles may enable effective intradermal vaccination from an adjuvanted patch delivery system. polyphosphazenes ͉ vaccine adjuvants

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

“…Microneedles have been fabricated by adapting manufacturing tools from the microelectronics industry to produce micron-scale needles that painlessly pierce the outer barrier layer of the skin to administer vaccine in a simple manner using a patch-like format. Microneedle patches are small and simple enough to use that they could be distributed through pharmacies or the mail and might be self-administered by patients (10) Solid microneedle patches have been coated with vaccines, including the model antigen ovalbumin (11), hepatitis B surface antigen (12), and inactivated influenza virus (13)(14)(15). In addition, hollow microneedles have previously been used to inject influenza vaccine into the skin of human subjects (16) and solid microneedles have been used to scrape the skin for delivery of DNA and other vaccines (17), although these methods do not lend themselves as easily to rapid distribution or self-administration.…”

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

“…It is a water-soluble molecule, which can be easily formulated with proteins and has the capacity to dissolve in a highly hydrated environment. Owing to this dual functionality of PCPP (as an adjuvant and film-forming nature), it is one of the most promising materials available for use in vaccine delivery [82].…”

Enhancement of skin permeation of vitamin C using vibrating microneedles

“…[2,7] Microneedles have been designed to be coated with the drug or to encapsulate the drug for release into the skin by dissolution. [8][9][10][11] Hollow microneedles have been coupled with a syringe for active drug infusion. [12][13][14] L-Ascorbic acid (vitamin C), a representative water-soluble vitamin, has a variety of biological, pharmaceutical and dermatological functions; it promotes collagen biosynthesis, provides photoprotection, causes melanin reduction, scavenges free radicals, and enhances the immunity (antiviral effect).…”