Efficient nanoparticle-mediated needle-free transcutaneous vaccination via hair follicles requires adjuvantation

Abstract

In vaccine development, activating the immune system is the major challenge. In this perspective, transcutaneous immunization (TCI) offers an attractive approach due to the presence of abundant antigen presenting cells (APCs) such as Langerhans cells and dendritic cells. In particular transfollicular vaccination aims to deliver antigens to the abundant perifollicular APCs without compromising the SC barrier function. The present work clearly demonstrates the potential of transfollicular immunization as an approach to deliver antigens across intact skin following co-administration of nanoparticles with an adjuvant on intact skin as well as stimulating and modulating efficient humoral and cellular immune response according to the specific clinical needs. Conflict of interest:Claus Prior presentations:Parts of this study were presented on international conferences as listed below. There is no conflict of copy rights with these abstracts or proceedings.

Size-dependent penetration of nanoemulsions into epidermis and hair follicles: implications for transdermal delivery and immunization

“…The hair follicle provides both a rich pool of peri-follicular APCs and a permeable sites due to the absence of a SC barrier in the lower follicular orifice, facilitating antigen uptake (Figure 4) [20]. Recently, polymeric nanoparticles, smaller than 200 nm, have been found penetrating into the hair follicles and being captured by peri-follicular APCs [21–24]. But the skin should be pretreated with cyanoacrylate stripping to reduce the barrier due to the poor skin penetration of polymeric nanoparticles.…”

“…However, due to poor dermal permeation into the rigid structure, tape stripping or iontophoresis should be combined to facilitate transdermal delivery [21–23, 26]. Besides, adjuvants are necessary to be combined with nanoparticles to generate efficient immune responses [24]. …”

Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

“…A 2-phased reaction of skin to barrier disruption has been described [39]. Some authors found a Th2- and eosinophil-focused response after tape stripping as well as increased IgG titters of anti-ovalbumin after application of a correspondent vaccine when applied on tape-stripped skin [38,40,41]. In this context different vaccine formulations might be worth comparing since other findings suggest higher antigen amount distribution to the hair follicle when the compound is encapsulated in nanoparticles [42].…”

Not Just for Tumor Targeting: Unmet Medical Needs and Opportunities for Nanomedicine

“…In a relevant mouse model we could recently demonstrate that transfollicular delivery of ovalbumin using polymeric nanoparticles (NPs) may lead to a significant cellular and humoral immune response, without compromising the SC barrier by any pretreatment, provided this nanotechnology approach is combined with some innovative adjuvantation [69][70][71]. This is another example for the potential of nanomedicine to effectively address the immune system (compare with the section 'Nanocarriers interfering with the immune system').…”