Safety, tolerability and efficacy of intradermal rabies immunization with DebioJect™

Abstract

In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes.

Real-time intradermal continuous glucose monitoring using a minimally invasive microneedle-based system

“…The microneedle geometry was previously developed to have a sharp tip geometry for easy penetration and a side opening to avoid tissue clogging the lumen during insertion (Roxhed et al 2007 ). The same microneedles were previously successfully used for insulin delivery (Roxhed et al 2008 ), as well as intradermal injection of rabies vaccine in humans in a clinical study (Vescovo et al 2017 ).…”

Current trends in polymer microneedle for transdermal drug delivery

“… Company Marketed product Features Reference 1 Valeritas Inc., Bridgewater, NJ, USA V-Go A disposable insulin delivery device ( Knutsen et al, 2015 , Raina et al, 2017 ). 2 Zosano pharma Inc., United States Adhesive Dermally Applied Microarray (ADAM) Utilizing for delivery of zolmitriptan ( Kellerman et al, 2017 , Spierings et al, 2018 ) 3 Sanofi Pasteur, Swiftwater, PA, USA Fluzone® Intradermal Quadrivalent Used for delivery of the seasonal influenza vaccine ( US,2020 ) 4 Debioject DebioJect™ This MN can be connected to any standard syringes to ensure the full penetration of the microneedle into the skin ( Vescovo et al, 2017 ) 5 Becton Dickinson, Franklin Lakes, NJ, USA BD Soluvia™ The first hollow microneedle product approved for vaccination ( Beran et al, 2009 , Donnelly et al, 2012b ) 6 NanoPass Technologies MicronJet™ It is a single-use, microneedle-based device for intradermal delivery of drugs, proteins and vaccines ( Donnelly et al, 2012b , Ita, 2015b ) 7 Nano BioSciences AdminPatch® Microneedle Arrays This MN allows continuous delivery of drugs by laminated the transdermal patch on the back surface of the microneedles ( Donnelly et al, 2012b ) 8 DermaIndia, Chennai, India Dermaroller® microneedlerollers This MN helps to treat some skin conditions ( Nalluri et al, 2015 ) …”

Enhanced immunity in intradermal vaccination by novel hollow microneedles

“…In contrast to a delivery hole at the needle tip, which compresses the tissue, a side‐outlet could minimize the potential for clogging by skin tissue and body fluids. Liquid thus diffused with little resistance in parallel to the skin surface . The fabrication method described here ensures the adjustment of needle length, and the position and orientation of the side hole, thereby delivering vaccine to the desired area of skin.…”

“…Antibody production with small doses of vaccine suggested effective delivery of antigen into the upper dermis by microneedles, leading to activation of immunocompetent DCs residing there. One successful example is the DebioJect system ™ (Bioject Medical Technologies; Portland, OR, USA), in which the microneedle is made of silicon with single or multiple delivery holes placed circumferentially . Delivery of vaccine with this system provided encouraging clinical results.…”