Immunization by Application of DNA Vaccine onto a Skin Area Wherein the Hair Follicles Have Been Induced into Anagen-onset Stage

Shaker, Dalia S.; Sloat, Brian R.; Le, Uyen; Löhr, Christiane V.; Yanasarn, Nijaporn; Fischer, Kay A.; Cui, Zhengrong

doi:10.1038/sj.mt.6300286

Cited by 20 publications

(27 citation statements)

References 35 publications

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“…14 At least for DNA vaccines the hair cycle state also seems to determine the successful transfection. 15 Inside the hair follicles antigen uptake by the rich pool of peri-follicular antigen presenting cells (APCs) is facilitated due to the absence of a SC barrier in the lower follicular orifice. 16 Therefore this delivery strategy very attractive for antigen encapsulation.…”

Section: Nanoparticles For Transfollicular Vaccinationmentioning

confidence: 99%

Particle based vaccine formulations for transcutaneous immunization

Mittal

Raber

Lehr

et al. 2013

Human Vaccines & Immunotherapeutics

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Vaccine formulations on the basis of nano- (NP) or microparticles (MP) can solve issues with stabilization, controlled release, and poor immunogenicity of antigens. Likewise transcutaneous immunization (TCI) promises superior immunogenicity as well as the advantages of needle-free application compared with conventional intramuscular injections. Thus the combination of both strategies seems to be a very valuable approach. However, until now TCI using particle based vaccine formulations has made no impact on medical practice. One of the main difficulties is that NPs and MPs cannot penetrate the skin to an extent that would allow the application of the required dose of antigen. This is due to the formidable stratum corneum (SC) barrier, the limited amount of antigen in the formulation and often an insufficient immunogenicity. A multitude of strategies are currently under investigation to overcome these issues. We highlight selected methods presenting a spectrum of solutions ranging from transfollicular delivery, to devices disrupting the SC barrier and the combination of particle based vaccines with adjuvants discussing their advantages and shortcomings. Some of these are currently at an experimental state while others are already in clinical testing. All methods have been shown to be capable of transcutaneous antigen delivery.

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Section: Nanoparticles For Transfollicular Vaccinationmentioning

confidence: 99%

Particle based vaccine formulations for transcutaneous immunization

Mittal

Raber

Lehr

et al. 2013

Human Vaccines & Immunotherapeutics

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“…5 However, TF vaccination is usually performed after pre-treating the skin area by plucking hairs, waxing or cyanoacrylate (superglue) stripping. [6][7][8] Pre-treatment not only permeabilizes the skin by removing the upper layers of the SC, but also activates the innate immune system. 1 While both factors probably improve the immunogenicity of a topically applied vaccine, the disadvantage of the method is that permeabilization of the skin increases considerably the risk of infections.…”

Section: Introductionmentioning

confidence: 99%

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

Mittal

Schulze

Ebensen

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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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.

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“…Fan et al (1999) reported that functional hair follicles were required for a topically applied DNA vaccine to induce immune responses [11]. Based on the aforementioned findings, we hypothesized, and provided data to support, that transcutaneous immunization by applying plasmid DNA onto a skin area wherein the hair follicles were induced into growth stage by hair plucking elicited a stronger antibody response than when the hair follicles in the application area were in the resting stage [15]. …”

Section: Introductionmentioning

confidence: 86%

“…The levels of anti-PA and anti-gp160 in serum samples were determined using ELISA [15]. Briefly, EIA/RIA flat bottom, medium binding, polystyrene, 96-well plates (Corning-Costar, Corning, NY) were coated with 100 ng of PA (List Biological) or the gp140 protein (NIH AIDS Research & Reference Reagent Program) dissolved in 100 µL carbonated buffer (0.1 M, pH 9.6) at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

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Transcutaneous DNA immunization following waxing-based hair depilation

Sloat

Kiguchi

Xiao

et al. 2012

Journal of Controlled Release

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Transcutaneous DNA immunization is an attractive immunization approach. Previously, we reported that transcutaneous immunization by applying plasmid DNA onto a skin area wherein the hair follicles had been induced into growth stage by ‘cold’ waxing-based hair plucking significantly enhanced the resultant immune responses. In the present study, using a plasmid that encodes the Bacillus anthracis protective antigen (PA63) gene fragment, it was shown that the anti-PA63 antibody responses induced by applying the plasmid onto a skin area where the hair was plucked by ‘warm’ waxing were significantly stronger than by ‘cold’ waxing, very likely because the ‘warm’ waxing-based hair depilation significantly i) enhanced the uptake (or retention) of the plasmid in the application area and ii) enhanced the expression of the transfected gene in the follicular and interfollicular epidermis in the skin. The antibody response induced by transcutaneous DNA immunization was hair cycle dependent, because the plasmid needed to be applied within 5 days after the hair plucking to induce a strong antibody response. The antibody responses were not affected by whether the expressed PA63 protein, as an antigen, was secreted or cell surface bound. Finally, this strategy of enhancing the immune responses induced by transcutaneous DNA immunization following ‘warm’ waxing-based hair depilation was not limited to the PA63 as an antigen, because immunization with a plasmid that encodes the HIV-1 env gp160 gene induced a strong anti-gp160 response as well. Transcutaneous DNA immunization by modifying the hair follicle cycle may hold a great promise in inducing strong and functional immune responses.

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Immunization by Application of DNA Vaccine onto a Skin Area Wherein the Hair Follicles Have Been Induced into Anagen-onset Stage

Cited by 20 publications

References 35 publications

Particle based vaccine formulations for transcutaneous immunization

Particle based vaccine formulations for transcutaneous immunization

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

Transcutaneous DNA immunization following waxing-based hair depilation

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