Microstructured transdermal systems (MTS) are also suitable for vaccine delivery because the vaccine can be delivered in close
proximity to the antigen-presenting cells in the epidermis, and thus it is possible to achieve excellent immune response with
smaller quantities of antigen than used in subcutaneous injection. The small size of microstructures causes comparatively
less mechanical trauma to the skin and these are painless upon insertion. Arrays of microstructures are typically held within
a patch that secures them against the skin. In the solid-coated microstructures the vaccine coats their exterior surface and
is released once these penetrate the skin.9
Electroporation is increasingly used for DNA vaccine administration in clinical trials, although, this is not a method of
needle-free delivery as it uses an electric shock to increase the efficiency of uptake of injected DNA. Applying an electric
pulse is a common technique in the laboratory for getting DNA into a variety of cells, and this approach has been scaled up
in portable machines for use on humans and livestock. Portable devices have been developed consisting of an array of electrodes
that deliver an electric shock to the skin at the point where a DNA vaccine solution has been injected, resulting in up to
100-fold improvement in efficiency over using a needle alone to deliver naked DNA.
The TriGrid delivery system developed by Ichor Medical Systems combines the injection and electric pulse in a single device.
The MedPulser DNA electroporation therapy system from Inovio Biomedical Corporation is used to deliver the pulse following
an injection. These systems have been evaluated successfully using a range of DNA vaccines. However, the continued reliance
on needles, the additional requirement for a source of electricity, and the discomfort of administration is likely to restrict
electroporation to DNA vaccine applications.
Oral delivery of therapeutics and vaccines is a promising approach to improve compliance with vaccination regimes. However,
because of the hostile environment of the stomach and the GI tract, antigens—particularly protein antigens—must be protected
to enable them to reach the site of absorption. One strategy is to encase the protein antigens in lipid molecules or lectins.
Elan Pharmaceuticals has demonstrated the use of a ligand (Ulex europaeus agglutinin I) that binds specifically to oligosaccharides
on M cells in the GI tract to deliver polystyrene microparticles and polymerized liposomes in a mouse gut loop model.10 In principle, these can be loaded with an antigen for targeted oral vaccine delivery.
Live Bacterial Vaccines
An alternative method of oral vaccine delivery is to develop live bacterial vaccines that can carry foreign antigens, either
as recombinant protein or DNA vaccines.2,5,6 The bacteria used for this naturally invade the gut and target inductive sites of the host immune system, such as mucosal
surfaces and antigen-presenting cells. These vaccines can induce cellular immunity and humoral responses to the heterologous
antigens that they carry (See Figure 1).
Using live attenuated bacteria as the basis of a vaccine is not a new concept. Attenuated Salmonella enterica serovar Typhi, administered as acid resistant capsules, is used as a vaccine against typhoid, and attenuated Vibrio cholorae forms the basis of a vaccine against cholera. However, the possibility of using attenuated bacteria as a vehicle for delivering
antigens against pathogens other than themselves is still being researched.5,6,11
The benefits of this approach are wide ranging. Live bacterial vaccines are relatively inexpensive to manufacture as the problems
and costs associated with antigen purification are avoided. Also, they are easy to administer and are stable at room temperature,
eliminating the need for cold storage. In addition, the bacteria are naturally immunogenic, removing the need to include an
adjuvant in any vaccine formulation. Another benefit of administering live bacterial vaccines is that they have some ability
to reproduce as they travel through the digestive system, thus increasing the dose beyond what is initially delivered.