Benefits of intradermal delivery/desirable attributes of intradermal delivery devices

Source/aims:

Based on 'Intradermal delivery of vaccines' - a review of the literature and the potential for development for use in low and middle-income countries - 27 August 2009 - WHO Optimize webpage: direct link to report (large PDF)

Prepared to support 'Consultation for the Program for Appropriate Technology in Health (PATH) : Intradermal delivery of vaccines for use in low- and middle-income countries - research and development strategy'.

Summary of potential benefits of intradermal delivery (IDD) of vaccines

Potential benefits of intradermal devices

 

1. Increased immunogenicity

The dermis and epidermis of human skin are extremely rich in various resident and recruited types of dendritic cells, a professional antigen-presenting cell capable of stimulating both innate and adaptive (i.e. antigen-specific) immune responses.

Consequently, it has been proposed that targeting the skin with vaccine antigens by using intradermal (ID) delivery could generate potent immune responses that are quantitatively or qualitatively superior to those generated with intramuscular (IM) or subcutaneous (SC) routes of administration.

If the ID route is superior to IM/SC routes, it might be possible to induce protective responses with lower doses of antigen, without the use of adjuvants and/or in populations that currently mount a poor response to some vaccines, e.g. influenza vaccine in older people and hepatitis B vaccine in patients with chronic renal disease.

If the skin is only equivalent to IM/SC routes in terms of generating immune responses to vaccines, other benefits of some of the devices being developed for use with the ID route are still possible such as increased patient acceptability, ease of use, lower storage/transport costs (especially in the cold chain), increased safety and reduced medical waste.

2. Dose-sparing

If the human skin does have superior properties to underlying subcutaneous and muscle tissue for the induction of immune responses to vaccine antigens, it should be possible to reduce the dose of antigen administered (including those encoded by DNA vaccines), while still inducing a protective immune response.

To date, most dose sparing has been achieved by simply reducing the volume of the standard formulation of liquid vaccine administered from 0.5 or 1.0 ml (for a standard IM/SC injection) to 0.1 ml for ID; this aims to achieve equivalent immunogenicity with only 10-20% of the usual dose.

If successful, this could have benefits for low- and middle-income countries in terms of potentially reducing the cost of vaccines, increasing availability of vaccines that have limited manufacturing capacity, and providing more effective vaccination. If a lower volume per dose is also achieved, this could reduce the storage volumes required in the cold chain.

3. Costs per dose – potential to reduce costs

If the ID route is superior to IM/SC routes and dose-sparing of vaccine antigen is achieved, then the cost of antigen per vaccine dose will be reduced.

Even if the antigen dose can not be reduced, it is possible that lower costs per dose could be achieved by the use of ID devices in development that aim to reduce other costs of vaccination including lower storage/transportation costs, safer vaccination, easier or faster administration (including self-administration) and reduced medical waste.

4. Volume in cold chain – potential to reduce volumes for transport/storage

If the ID is route is superior to IM/SC routes and dose-sparing is achieved, the volume of antigen per dose might also be reduced, thereby reducing the volume of vaccine to be transported and stored in the cold chain.

This could be achievable with existing formulations and presentations of some vaccines as each (multi-dose) vial would therefore contain more usable doses. This is not likely to be possible with pre-filled syringe formulations for safety and practicality reasons.

Regardless of any dose-sparing impact, some, but not all, novel IDD devices (e.g. microneedle patches) would be expected to have a smaller packaged volume per dose of those components requiring refrigeration than existing vaccine presentations such as prefilled syringes. Thus, the demands for cold-chain capacity needed to store vaccines could be reduced by developing alternative delivery devices.

5. Medical waste – potential for reduction

The medical waste generated by vaccination exposes health care workers, waste handlers, patients and the community at large to infection, injuries, and risks of polluting the environment. Use of the ID route for vaccines will not reduce waste per se but safe and easy disposal is likely to be built into the design criteria for novel IDD devices.

6. Acceptability of vaccines – potential for increased uptake

There are complex reasons why the rate of vaccination uptake is not ideal in some populations but the 'acceptability' of vaccines by the vaccinee and/or parent/guardian is an important contributor.

At least some of the ID devices in development aim to be more acceptable to patients than IM/SC routes, mostly by reducing pain or discomfort at the time of vaccination. Subsequent local or systemic events tend to be vaccine-specific but a reduction in antigen-dose or need for adjuvants by the use of the ID route could reduce local or systemic reactogenicity.

7. Administration – potential to improve ease of use

BCG is delivered ID using the Mantoux technique with a tuberculin syringe and needle. This method is generally considered to require considerable training to do well and there is probably significant variability in the dose delivered. Several novel ID devices aim to reduce the training needs for ID delivery and to increase reliability of dose delivered, and to the right skin layers. Some of the devices in development might also be suitable for self administration.

8. Integration/separation of vaccine and device
9. Safety – potential to reduce needle-stick injuries

Vaccination is associated with risk to the vaccinee, the vaccinator and also to others in the chain of medical waste disposal. Risks include mal-administration of vaccine (wrong or contaminated vaccine, wrong dose, wrong route) accidental needle-stick injuries with either 'clean vaccine' or, more likely, contaminated with the previous vaccinee's blood/tissue fluids (the risk is usually to the vaccinator but it can be to subsequent vaccinees), 'deliberate' needle-stick injury with contaminated vaccine, due to needle/syringe re-use (e.g. in injected drug users or due to inadequate clinical supplies/control).

Several of the IDD devices being developed are integrated with the vaccine reducing 'wrong or contaminated vaccine' issues, or are needle-free and could, therefore, reduce the risk of needle-stick injury or needle and syringe misuse. Other needle-dependent IDD devices are probably less likely to cause sharps injuries than conventional needle and syringes due to the incorporation of guards or having shorter (micro) needles including ones that are integrated with the syringe/patch.

Another important attribute is the simplification of medical waste disposal, which can reduce several risks of vaccination and environmental contamination.

10. Compatibility with liquid vaccine

Most injected vaccines are in a liquid presentation or are reconstituted from a lyophilized powder immediately before administration. Devices that are compatible with liquid vaccines (e.g. intradermal needles, depth-limiting adaptors, jet injectors, hollow microneedles on patches/syringes) are likely to require less re-formulation and therefore potentially could be more straightforward to develop than those that require a solid-phase vaccine at the time of administration (e.g. solid, coated microneedles).

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Last updated: 13 October 2010