Intradermal (ID) vaccination is gaining increased attention in a scientific context, due to its dose-sparing potential and improved immunogenicity. However, the currently used Mantoux technique for ID injection requires a high amount of expertise and is perceived as painful by patients. To encounter these issues a newly TM proto-device VAX-ID is developed. New insights in dermal thickness were needed to determine the maximum penetration depth and consequently the needle characteristics. The aims of the study were to investigate: 1) the thickness of the upper two skin layers (e.g. epidermis and dermis) at the proximal ventral and dorsal forearm and deltoid in adults aged 18 – 65 years; 2) the penetration TM depth of the needle and the injected volume of VAX-ID in human tissue samples.

1. Intradermal (ID) vaccination is gaining increased attention in a scientific context, due to its dose-sparing
potential and improved immunogenicity. However, the currently used Mantoux technique for ID injection
requires a high amount of expertise and is perceived as painful by patients. To encounter these issues a newly
TM
proto-device VAX-ID is developed. New insights in dermal thickness were needed to determine the
maximumpenetrationdepthandconsequentlytheneedlecharacteristics.
The aims of the study were to investigate: 1) the thickness of the upper two skin layers (e.g. epidermis and
dermis) at the proximal ventral and dorsal forearm and deltoid in adults aged 18 – 65 years; 2) the penetration
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depthoftheneedleandtheinjectedvolumeofVAX-ID inhumantissuesamples.
High-frequency ultrasound (HF-US, VEVO® 2100, Visualsonincs Inc., 40Mhz) was used as imaging technique
for the investigation of the penetration depth and the injected fluid as also for the measurement of the skin
thickness.
The thickness of the epidermis and dermis was measured through ultrasound images. Both the proximal
dorsal and ventral forearm were divided into three sections of 4.5cm, each resulting in 90 frames. The
distances were measured on a frame, every 7.5mm. The deltoid region consisted of 1 section of 8 frames.
Distances were measured by drawing straight lines perpendicular from the skin surface to the dermal –
hypodermaljunction.
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Injections with VAX-ID (31G needle and 0.10cc methylene blue), were performed on human skin samples,
obtainedafterplannedsurgicaloperation(e.g.abdominoplasty).Animagingholderwasdesignedtoplacethe
ultrasoundprobeperpendiculartothefattissue.Thisholderwasdevelopedtoblockthedeviceinitsactivated
positionwiththeneedlethroughtheskin.
First results (n=50 volunteers) showed an overall mean skin thickness of 1.46mm (0.89-2.74mm) at the
proximal dorsal forearm, 1.23mm (0.65-2.34mm) at the proximal ventral forearm and 2.17mm (0.90-
3.70mm) at the deltoid. Mean thickness of proximal dorsal and ventral forearm and deltoid were significantly
different for men vs women (p= 0.008; <.001; 0.002), whereas minimum thickness differed significantly for
proximal ventral forearm and deltoid (p= 0.002, 0.005). No correlation was found between age and skin
thickness.
Injectionsinhumantissuesamplesshowedthatthefluidcouldmainlyberetrievedinthedermisandthatbleb
formation was seen at the injection site. Leakage to the hypodermis or the epidermis was difficult to assess
withHF-US.
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TheimagingtestsshowedthattheVAX-ID prototypesusedwereabletoinjectinthedermallayeroftheskin.
Although analysis of the penetration depth of the needle was not possible yet, injected volumes showed
satisfying depths, next to bleb formation which is an objective indication of correct ID injection. Additional
research using e.g. histology and/ or micro-CT will be needed. Investigation of the skin thickness appears to
enable determining the most effective needle length to deliver fluid ID without leakage. However, a larger
samplesizeofbothmenandwomenwillbeneededtodrawfinalconclusions.
-ID
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Introduction
Method
Results
Conclusion
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HF-Ultrasound to assess skin thickness and accuracy of penetration depth of VAX-ID
1,2,3,* 4,5 6 6 1 7 7 1,8 1,3
Timothi JS Van Mulder | Julio Jimenez | Manon de Koeijer | Stephanie Augustynen | Dimitri Willems | Marc Demolder | Guido De Meyer | Koen CL Beyers | Vanessa Vankerckhoven
1 Novosanis nv, Antwerp, Belgium | 2 Department of Nursing and Midwifery, University of Antwerp, Belgium | 3 Vaccine & Infectious Disease Institute, University of Antwerp, Belgium | 4 Department of Development and Regeneration, KU Leuven, Belgium | 5 Departament
of Obstetrics and Gynecology, Clinica Alemana, Santiago, Chile | 6 Department Clinical Molecular Sciences, Hasselt University, Belgium | 7 Department of Pharmaceutical Sciences, Laboratory of Physiopharmacology, University of Antwerp, Belgium | 8 Voxdale, Belgium
* Presenting author
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VAX-ID Device | Patent pending: PCT/EP2013/057990
Ultrasound picture of injected fluid in the dermal layer indicating layers:
This ultrasound image shows the different layers of the skin as well as the liquid depot. The fluid appears to be mostly injected in the
dermis, but leakage to the hypodermis or the epidermis isn't clear. To allow for assessing this, more tests are needed.
Ultrasound picture of injected fluid in the dermal layer indicating width and height:
This picture shows the height (Linear 1) and the width (Linear 2) of the injection depot in the dermal layer, indicated using
blue bars and lines.
Bleb formation on skin sample Ultrasound picture of bleb formation
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This injection was done without the imaging holder. VAX-ID was placed perpendicular to the skin, the injection was given
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and VAX-ID was removed. The appearance of bleb and leakage were recorded. We recorded a very clear bleb formation.
The ultrasound image of this injection shows the expanded dermis in the middle.
However, leakage of fluid to the hypodermis cannot be excluded.
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VAX-ID imaging holder
Contact: timothi.vanmulder@novosanis.com
Knowledge for Growth conference, Ghent, 2015
1 twist
to activate 2 make skin
contact 3 push plunger
to administer 4 needle
auto-retracts
needle penetrates
reservoir
plunger empties
reservoir
needle-stick safe
5 dispose of
device
one-time use only
reservoir sealfoot needleneedle hub spring plungerhousing
novosanis
DERMIS
HYPODERMIS
EPIDERMIS