Most vaccines are delivered by the intramuscular or subcutaneous routes using a needle and syringe; the intradermal route is only widely used for the administration of Bacille Calmette-Guerin and rabies vaccines. However there is renewed interest in intradermal vaccine delivery, driven by the fact that the dermis and epidermis of human skin are rich in antigen-presenting cells, suggesting that delivery of vaccines to these layers, rather than to muscle or subcutaneous tissue, should be more efficient and induce protective immune responses with smaller amounts of vaccine antigen.
Clinicaltrials investigating intradermal delivery and its potential for dose-sparing have been conducted with several different vaccines, with variable results. These have been reviewed in a recent report from the Program for Appropriate Technology in Health (PATH) and the World Health Organization (WHO). (2) For some vaccines, there has been a clear demonstration of dose-sparing by intradermal delivery; however, there ate several gaps in knowledge as well as developmental and operational challenges to overcome if the benefits of using intradermal delivery are to be fully realized.
Dose-sparing arising from intradermal delivery of vaccines could be beneficial to immunization programmes, particularly in resource-poor settings, by potentially reducing the per-injection cost (including transport and storage) of vaccines because more doses might be obtained from the existing vaccine presentation.
Dose-sparing might also "stretch" the availability of vaccines in cases where supply is limited by manufacturing capacity. This is probably most relevant for pandemic influenza vaccines where global production capacity limits access to a vaccine at the start of a pandemic. (3) In 2009, H1N1 vaccine was not available in most low-income countries until 8 months after WHO's declaration of the influenza pandemic. (4)
Other vaccines with potential supply constraints include yellow fever and inactivated poliovirus vaccines. (5,6) The level of demand for inactivated poliovirus vaccine in the period following eradication of wild-type polioviruses and the end of the use of oral poliovirus vaccines is uncertain, but modelling suggests that there could be a "demand spike" and supply shortage of. inactivated poliovirus vaccine during this period. (6)
New delivery devices
New devices for easier, more reliable intradermal delivery as alternatives to the currently used Mantoux technique ate being developed. (2,7) Some of the devices such as disposable-syringe jet injectors ate needle-free and could therefore reduce of eliminate needlestick injuries and the costs associated with their treatment, estimated at USS 535 million per year worldwide. (8) Other intradermal delivery devices such as microneedle patches are likely to occupy less volume than vials of prefilled syringes, thereby reducing demands on cold-chain capacity.
Current clinical research
The recent PATH and WHO report reviewed more than 90 clinical trials of intradermal delivery with vaccines against 11 diseases. (2) For some vaccines, notably influenza and rabies vaccines, intradermal delivery of reduced doses resulted in equivalent immune responses to the standard dose delivered by the standard route. Data from trials with hepatitis B vaccine were more variable, but also regarded as encouraging. (9) Promising data demonstrating dose-sparing have also been obtained with other vaccines including inactivated poliovirus, yellow fever and hepatitis A vaccines. (2)
Results from clinicaltrials publishcd since the completion of the report provide further evidence for dose-sparing using the intradermal route. One study compared equivalent doses of modified vaccinia Ankara delivered by subcutaneous, intramuscular and intradermal routes; equivalent immune responses and protection against vaccinia-virus challenge were induced with intradermal doses ten-fold lower than those delivered by intramuscular or subcutaneous injection. …