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Hair follicles are a shortcut to circumvent the stratum corneum barrier
One of the main obstacles for any attempt at transdermal delivery is the stratum corneum (SC) barrier. For the purpose of transcutaneous immunization (TCI), that is, needle-free administration of vaccines via the skin [1], neither naked vaccine antigens nor the conventional vaccine formulations can overcome healthy human SC to an extent that would allow the successful delivery of the required dose of antigen. A simple way to circumvent this obstacle is intradermal injection of the vaccine which may be done in a reproducible way by employing special adaptors to standardize injection depth and angle, special injection techniques or a prefilled microsyringe applicator (e.g., Soluvia BD). Other barrier reducing methods (e.g., microneedles, jet injection, dry powder injectors, skin abrasion) are being explored as well. Nonetheless, needle-free vaccination strategies are generally preferred in order to avoid the risk of infection after breaking the SC barrier and the risk of distributing contagious diseases by sharing needles.
TCI combines the advantages of other routes of mucosal vaccination using needle-free strategies being efficient, safe, convenient and economical. In general, mucosal immunization is superior to the conventional intramuscular or subcutaneous injection of vaccines due to the higher number of antigen-presenting cells (APC) which are patrolling the interfaces of the body to the environment in order to build a first line of defense against the invasion of pathogens and thus prevent disease before its onset.
Transfollicular delivery is being explored as an alternative route for vaccine delivery [2-5]. Some experiments hint that transfollicular vaccination may favor a CD8+ biased response which would be promising for developing vaccines against intracellular pathogens, cancer or virus infections [3]. Hair follicles (HF) represent shunt pathways across the SC [6]. In transfollicular vaccination, antigen-loaded nanocarriers shall be trafficked across the HF to reach the large numbers of perifollicular Langerhans cells which may serve as APC [7]. As with glands and other invaginations of the skin, HF contain high numbers of commensal microbes. Therefore, it is not surprising that some special defenses have evolved in order to prevent the invasion of pathogens into the body as well as avoid an overreaction of the immune system to their constant presence. As especially the lower HF has...