ABSTRACT
Prophylactic vaccines are one of the most cost-effective ways of preventing illness and death from infectious disease. The
public health benefit of this approach, however, is dependent on the proportion of the at-risk population that is vaccinated.
The frequent need for more than one dose of vaccine to offer protection and the unfriendly method of administration—commonly
needle and syringe—means that compliance with vaccination programs is an ongoing problem. In addition, the use of sharps can
lead to public health problems, particularly where safe disposal of hazardous waste is not readily available. There is an
increasing interest in alternative delivery mechanisms for antigens, and many companies are developing needle-free approaches.
This article will review some of the technologies that aim to revolutionize vaccine administration by focusing on oral vaccine
delivery using live bacteria.
The demand for new and improved vaccines against human diseases is rising and the interest in developing new delivery mechanisms
for antigens is increasing concurrently.1–4 Needle-free vaccinations offer the advantage of convenience, and remove the need for sharps, which can cause public health
problems. Many companies, therefore, are focusing on developing alternative transdermal and oral vaccination methods.
Mechanisms for transdermal delivery include needle-free devices that deliver solid or liquid formulations of vaccines. Oral
delivery of protein antigens presents major challenges because of the strong natural barriers along the gastrointestinal (GI)
tract, including stomach acid and proteases that can degrade these molecules. Moreover, the rate of absorption of proteins
along the GI tract is often poor. Encasing protein antigens with lipid molecules to deliver them through the hostile environment
of the stomach and releasing them in the intestine is one approach to address these problems. An alternative approach is the
development of live bacterial vaccines that carry foreign antigens.2,5,6
Live bacterial vaccines are relatively inexpensive to manufacture, room temperature stable, easy to administer, and offer
the added benefit of being inherently immunogenic.
Transdermal Delivery
The skin immune system arises from cellular and humeral components of the epidermis and the dermis. Among the most important
components of the skin immune system are the Langerhans cells, which are specialized antigen presenting cells found in the
viable epidermis. The Langerhans cells detect and internalize antigens, and carry them to draining lymph nodes where they
are presented to T-cells, invoking an immune response.
Jet injectors, such as Antares Pharma's Medi-Jector VISION, deliver medication through high-speed, pressurized liquid penetration
of the skin without a needle. These have been developed as single-use devices and multiuse systems. A high peak pressure behind
the liquid is required so it can drill a hole in the skin, and then the pressure is reduced to allow the rest of the liquid
to enter the skin. These pressures need to be carefully controlled. The difficulty in doing this and the cost attached to
the various solutions are some of the reasons why jet injectors are not used more widely.7
Other transdermal approaches deliver the antigen in a solid form. These approaches have the added benefit that the therapeutic
agent is more stable and therefore may not need cold storage. PowderMed, which was acquired by Pfizer in October 2006, uses
its PMED delivery device to propel gold particles coated in a DNA vaccine into the skin using high-pressure helium. This approach
delivers the DNA directly to Langerhans cells, thereby stimulating immunity. The device is pain free, and reportedly can be
administered without the need for trained medical personnel. This is particularly important given that one of the vaccines
in development is against pandemic avian influenza.8
A third approach uses the pharmaceutical formulation itself to puncture the skin. Glide Pharma has developed a low-velocity,
spring-powered administrator that pushes a pointed rod of pharmaceutical material through the skin in a fraction of a second.
This administrator enables constant, reliable delivery of a solid dosage form and could be applied to various vaccines. The
low cost of manufacturing the device is an added bonus, which further supports its use in developing countries.7
