CHICAGO – Of all the novel cutaneous delivery methods being studied for vaccine administration, noninvasive patchlike systems appear to offer the most advantages, according to Dr. Bruce G. Weniger.
"This is maybe 5 or 10 years off in the future, but this method could be painless upon delivery of antigen on either coated solid microneedles or within dissolving microneedles only to the epidermis, which lacks nerve endings," Dr. Weniger said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Dr. Bruce G. Weniger
"In theory, it can also be very space efficient for cold chain volume constraints, which is a serious problem as the new prefilled, single-dose packagings for rotavirus vaccine are taking up scarce space in the developing-world vaccine refrigerators. Moreover, such Band-Aid–like delivery systems (called "plasters" in British parlance) are potentially thermostable outside the cold chain. They may be cheaper than needle syringes to dispose of as nonhazardous waste, and in some cases there may be no complex, reusable applicator device to buy, transport, maintain, break, or lose."
Speaking at a later symposium on novel vaccination strategies, Dr. Weniger, an associate editor at the journal Vaccine, and retired former lead for vaccine technology at the Centers for Disease Control and Prevention (CDC), reported that cutaneous vaccination often produced better immune responses than deposition into deeper tissues, thus in some cases permitting dose sparing when vaccine may be scarce or expensive.
He also noted that some new methods of vaccine delivery into or onto the skin – but not patches – share one advantage of the traditional Mantoux method, now used for tuberculosis skin testing and BCG vaccine: the use of existing off-the-shelf vaccines. "The disadvantages of this 100-year-old method are that it’s difficult to do correctly, and local reactions are often more frequent and may be unacceptable if the vaccine contains an irritating adjuvant," he said. "It’s also uncomfortable for the patient."
Newtown, Pa.–based SID Technologies is developing an intradermal injection adapter that attaches to a conventional tuberculin/insulin syringe "to make the Mantoux injection method foolproof," Dr. Weniger said. "Just push it in, and it guides you consistently to the desired bleb or wheal."
The company, which received Small Business Innovation Research (SBIR) funding from the CDC for the technology, is working with West Pharmaceuticals for the developed-world market and with PATH (Program for Appropriate Technology in Health), a Seattle-based nonprofit organization, "to bring this to the developing world for potential cost-saving intradermal administration of expensive rabies and polio vaccines," he said at the meeting, sponsored by the American Society for Microbiology.
The Bioject ID Pen needle-free jet injector, developed by Portland, Ore.–based Bioject Medical Technologies, is anticipated to receive clearance from the Food and Drug Administration (FDA) this year for intradermal delivery. Dr. Weniger described this device as "small, light, powered by metal springs, and featuring single-use autodisabling syringes for 0.05- or 0.1-mL volumes." Studies supported by PATH and the World Health Organization are evaluating its use for delivering rabies and polio vaccines in developing countries.
Another spring-action jet injector product, PharmaJet’s intradermal (ID) model, which also received CDC SBIR contract support, was granted FDA 510(k) clearance in 2011. According to Dr. Weniger, this device, manufactured by Golden Colo.–based PharmaJet, is being used to intradermally administer one of the four candidate dengue vaccines under study in the world. It has been tested in primates, and human trials were launched in 2010. Other clinical trials of the PharmaJet ID are underway in India for delivering rabies and polio vaccines.
The various techniques for cutaneous delivery of vaccines fall into the following categories:
• Mechanical disruption of the stratum corneum. "There are a variety of methods that are used to basically scrape off or abrade that dead layer of skin to allow the vaccine in," explained Dr. Weniger, who is now on the faculty of Chiang Mai University in Thailand. "You can even use cellophane tape applied to the skin and just pull it off a few times. Some researchers have even applied cyanoacrylate superglue and ripped that off, which is probably not painless, he added. There are also microscopic projections which are used to scrape the skin before you apply a drop of vaccine, and you can even use sandpaper friction."
• Coated solid microneedles. This technology involves coating dried vaccines onto microprojections. "When it’s put into the body, within the first few seconds or minutes, the moisture of the body dissolves the vaccine and it begins to be taken up by antigen-processing cells," Dr. Weniger said. "There are but a few human trials to date of which I’m becoming aware."