Transdermal immunization

A. Paul and G. Cevc, Non-invasive administration of protein antigens transdermal immunization with the bovine serum albumin in transfersomes, Vaccine Res. 4 145 (1995). 

A. Paul, G. Cevc, and B. K. Bachhawat. Transdermal immunization with large proteins by means of ultradeformable drug carriers. Eur. J. Immunol. 25 3521-5324 (1995). 

The route of administration influences the likelihood of an antibody response independent of the mechanism of induction. The probability of an immune response is the highest with subcutaneous administration, less probable after intramuscular administration and intravenous administration is the least immunogenic route. There are no studies comparing parenteral and nonparenteral routes of administration. Flowever, as both mucosal tissues and the skin are immune competent organs designed to keep invaders out of the body, intranasal, pulmonary, and transdermal administration of therapeutic proteins may increase the risk of an immune response as compared to parenteral routes. 

Transdermal delivery of proteins and/or DNA vaccines for needle-free immunization has been attracting increasing interest. Cui et al. [110] reported on ethanol-in-fluorocarbone (E/F) MEs for topical immunisation. The authors showed that plasmid DNA incorporated into E/F MEs was found to be stable. Furthermore, after topical application to the skin, significant enhancements in luciferase expression, antibody production, and T-helper type 1 based immune response compared to an aqueous or ethanolic solutions of DNA were observed [110]. 

In recent years, the potential of using the skin for vaccination purposes has reoeived a great deal of attention [132], One of the more promising ways of enhanoing skin permeability to enable transdermal transport of large moleoules or oomplexes for transou-taneous immunization is sonophoresis. 

The success of vaccination depends primarily on the method of presenting the antigen to the host immune system. Antigens have usually been delivered by parenteral (such as intravenous, intramuscular, intraperito-neal, intradermal, and subcutaneous) administration, but recent studies have shown that other routes of delivery such as intranasal, oral, and transdermal delivery have also been effective. In some cases, vaccination through mucosal routes resulted in better responses in IgA production. Because non-parenteral vaccine delivery presents many obvious advantages, numerous attempts have been made on the development of non-parenteral delivery of vaccines. 

Transdermal vaccination or transcutaneous immunization, is attractive, because it does not require specially trained personnel necessary for needle injections. Topical application of antigens to intact skin has shown promising results for the administration of DNA-based vaccines. Noninvasive gene delivery by pipetting adenovirus- or liposome-complexed plasmid DNA onto the outer layer of skin was able to achieve localized transgene expression within a restricted subset of skin in mice. It also elicited an immune response against the protein encoded by the DNA. ... 

Misra, A Ganga, S. Upadhyay, P. Needle-free, non-adjuvanted skin immunization by electroporation-enhanced transdermal delivery of diphtheria toxoid and a candidate peptide vaccine against hepatitis B virus. Vaccine 1999, 18, 517-523. 

Levy, J.G., Chowdhary, R., Ratkay, L., Waterfield, D., Obochi, M., Leong, S., Hunt, D., and Chan, A. (1994) Immune modulation using transdermal photodynamic therapy, in Photodynamic Therapy of Cancer II, Proc. SPIE 2325, Brault, D., Jori, G., Moan, J., and Ehrenberg, B. (Eds.), pp. 155-165, The International Society for Optical Engineering, Bellingham, WA. 

Vogler MA, Patterson K, Kamemoto L, Park J-G, Watts H, Aweeka F, KUngman KL, Cohn SE. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-l-infected women. Pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Dis 2010 55 473-82. 

No current device meets all of these parameters. Diffusion-controlled release is demonstrated by transdermal patches e.g., birth-control, nicotine, etc.), whereas particulates such as metallic micro-/nanoparticles have been used to ablate cancer cells by localized heating with near-IR light.Whereas normal blood vessels have pore sizes <100 nm, the vessels adjacent to cancer cells have pore sizes between 100 and 200 nm. Hence, if DDS particulates e.g.y liposomes, polymeric micelles, metallic nanoparticles) are of this size regime, they will automatically situate nearby cancer cells. However, it usually takes at least 1 day of blood circulation to accumulate sufficient amounts. In order to hide the particles from the immune system, the particulates must be covered with a stealth lipsome such as poly (ethyleneglycol), PEG otherwise, the particulates will be filtered out of the body via the liver as urine. 

Skin microporation is investigated for transdermal delivery of water-soluble small drugs and macromolecules such as proteins. It involves the creation of micron dimension transport pathways in the skin using a minimally invasive technique, such as microneedles, thermal microporation, or radiofrequency ablation. An applicator can be used to apply the microneedles on the skin to create the micropores followed by patch application. Alternatively, the drug can be coated directly on the microneedles. The latter approach has been used for vaccine delivery since the amount of protein antigen needed to generate immune response is very small and the dose can be accommodated by coating the microneedles [110]. 

In addition to the effects of cytokines on PDT-induced suppression of immune responses, it is important to consider the effect of PDT on the expression of immune molecules critical to immune system activation. Transdermal PDT was shown to inhibit the ability of Langerhans cells (LC) to stimulate alloreactive T-cells- - and LC treated ex vivo expressed lower levels of major histocompatibility (MHC) antigens and CD80 and CD86 costimulatory molecules, which are needed for T-cell activation. Additionally, in vitro PDT-treated murine DC had a reduced ability to stimulate alloreactive T-cells and exhibited lower levels of MHC molecules, costimulatory molecules, and adhesion molecules.- Thus, in addition to altering the function of APCs, PDT has the ability to disrupt the APC-T-cell cognate, which is needed for T-cell activation. 

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