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Millions of needles and syringes are used each day in health care. The World Health Organization (WHO) estimates that 12 billion injections are given each year. Only about 5% are used in the delivery of vaccines for immunization and prevention of infectious diseases. Even though vaccinations have saved lives over the years, there are some hurdles to overcome. One of these is the use of needles or "sharps" to deliver the vaccines.
According to Myron Levine of the Center for Vaccine Development, University of Maryland School of Medicine and member of the Global Alliance for Vaccines and Immunization (GAVI) "three fundamental themes remain in common worldwide: first, high immunization coverage of target populations generally must be attained for maximal public health impact; second, most current vaccines are administered parenterally using a needle and syringe; third, there is a broad recognition of the need to find ways to administer vaccines without the use of 'sharps' (that is, needles and syringes)."
The disadvantages of needle delivery of vaccine include:
(1) Pain and irritation of vaccination site. A large fraction of our population is scared of needles, probably as consequence of a previous bad experience. The majority of patients at the delivery end of vaccination are very young children under the age of two and needle pricks in this patient population can cause a lot of pain and distress. Needles may also cause discomfort at the injection site long after the shot has been applied.
(2) Lack of compliance. The World Health Organization's Expanded Programme on Immunization (EPI) has recommended six basic vaccines for infants in developing countries: diphtheria, pertussis, and tetanus toxoids (DPT), bacillus Calmette-Guerin (BCG), and attenuated polio and measles. In developed countries such as the US, more vaccinations are required by health authorities. However, for the so-called "herd immunity" to work, a certain % of the population must comply with vaccination schedule.
(3) Safety. Vaccination with needles produces dangerous infectious waste that come with serious health threats to both patient and health care professionals. The reuse of unsterilized needles has facilitated the transmission of blood-borne infections such as HIV and hepatitis.
(4) Speed and efficiency. Recently, the threats of bioterrorism and pandemic flu have highlighted the need of fast, easy and safe vaccine delivery to the masses should the need arise. Definitely, vaccination using syringes and needles was not designed for these situations.
(5) Cost-efficiency and logistics. Doing away with syringes and needles can make vaccinations in less developed countries cheaper and more accessible. Syringes and needles need to be transported and stored for vaccination purposes. Injectible vaccines need to be refrigerated during transport.
Although needle-free delivery systems exist for many drugs, vaccines present a challenge because they usually consist of large molecules that cannot be easily delivered transdermally. Myron Levine summarized in a review article the different methods of administrating needle-free vaccines.
(1) Vaccines delivered through mucosal surfaces. Though theoretically possible, this form of delivery hasn't caught on except perhaps with the use of the nasal spray.
(2) Oral vaccines. Specific vaccines can be given orally in the form of pills. Oral polio vaccine has already been around for awhile. Other vaccines can be delivered via this route including certain types of cholera vaccines and the new rotavirus vaccines. However, this delivery route presents some problems for very young infants who might not be able to swallow properly and whose digestive system may not be able to withstand the effects of the vaccines.
(3) Nasal vaccines. The nasal vaccine through the respiratory tract is a very popular alternative to the flu shot. The FluMist nasal spray, made from live, attenuated, cold-adapted vaccine, has been approved by the FDA and is delivered using a single-use spraying device through the nostrils.
(4) Aerosol vaccine. This mode of administration through the respiratory tract has been tested for measles vaccine. This is an alternative to the nasal spray and can be used with liquid aerosol and dry power for mass immunization.
(5) Needle-free percutaneous jet injection. This device works by propelling liquid through a small skin pore under high pressure. The liquid is then transported to the dermis and underlying tissues and muscles. There are multiple dose injectors available, making this type of delivery fast and practical for mass immunizations. However, it has the disadvantage of a high incidence of local irritation at the vaccination site as well as the possibility of transmission of infectious diseases.
(6) Transcutaneous delivery. This is commonly known as the "vaccine patch" and is delivered via the skin. The adhesive patch is applied after a preliminary hydration, directly on the skin. The occlusive patch makes the skin permeable to the vaccine. The cutaneously applied antigens are then taken up by Langerhans cells found in the upper layer (epidermis) of the skin allowing the immune-processing cells to migrate to the lymph nodes.
In recent years, several biotech companies have invested millions of dollars in developing, testing and finalizing different forms of needle-free delivery systems for all kinds of drugs, not only vaccines. The most promising of the needle-free vaccination systems at this juncture is Trans Cutaneuous Immunization (TCI).
Several advantages of the TCI have been identified. including cost-effective, safe, fast distribution, easy storage (can be stockpiled!) and easy administration, with the potential for self-administration.
In 2007, American researchers tested the efficacy of TCI with Clostridium difficile toxoid A in mice, with positive results. The bacteria C. difficile is the leading cause of nosocomial diarrhea, e.g. infectious diarrhea transmitted in the hospital setting. Also in 2007, Johns Hopkins University researchers tested the protective efficacy of TCI with the heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC). The results showed that the patch "induced anti-toxin immune responses that did not prevent but mitigated the illness.
Apollo Life Sciences has developed and patented a needle-free drug delivery and in May 2007 it released the results of preliminary studies on needle-free transdermal delivery of tetanus toxoid vaccine in mice. Apollo has developed the non-invasive transdermal carrier, TransD which works by delivering "a protein-laden water layer across the skin and into the surrounding dermal and sub-dermal layers. It has potential to replace injections for biodrugs based on molecules such as interferon, growth hormones and anti-TNF (tumor necrosis factor)."
The TCI developed by the biotech firm Iomai, now owned by the Austrian company Intercell has recently made the headlines. Drug Delivery Report described how it works: "Administration is a two-step process. First, the skin is prepared by placing the device on the patient's arm and pulling a tab. The tab draws a mildly abrasive substance across the skin, making a painless and nearly imperceptible dent and simultaneously leaving an ink mark to indicate where the patch should be applied. The patient then wears an adhesive patch [with the vaccine] for several hours." The innovative design company Ideo helped designed the patch which required removal of an extremely thin layer of skin (about one-thousandth of an inch!).
Currently, Intercell's vaccine patch against traveler's diarrhea or the so-called Montezuma's Revenge is showing promise. The disease is a major cause of diarrhea among travelers, with symptoms ranging from stomach cramps to vomiting and diarrhea. Dr. Herbert DuPont of the University of Texas is one of the researchers involved in testing the vaccine. He told Reuters: "I think it's one of the most exciting new developments in travel medicine. People could buy this and put it on themselves whenever they take a trip. It is the most convenient form of immunization I have ever seen."
The vaccine has been tested on visitors travelling to Guatemala and Mexico and showed 70% efficacy against traveler's diarrhea. In another field study of 170 travelers as part of the vaccine patch Phase II trials, the vaccine patch reduced the risk of developing moderate to severe traveler's diarrhea by 75%. Phase III clinical trials are in process. If approved, this will be the first vaccine to prevent traveler's diarrhea. The study results were published in the Lancet and conclude that "the vaccine patch is safe and feasible, with benefits to the rate and severity of travellers' diarrhea."
A second promising Intercell vaccine patch is targeted against the pandemic flu. If successful, the patch will expand the limited vaccine supplies by allowing fewer or lower doses of vaccine. The program is funded by a United States Department of Health and Human Services contract." The patch contains a vaccine made from the H5N1 influenza virus. Results of a Phase I/II trials showed that a small amount of the vaccine triggered a protective immune response in 73% of the study participants. Phase II trials are expected to begin in 2009.
Vaccination and immunization technology has changed a lot in recent years as it tries to meet the health challenges facing both developed and developing countries. The TCI or vaccine patch is a promising tool which will hopefully help solve some of the problems facing traditional vaccine delivery systems.
