Elsevier

Methods

Volume 31, Issue 3, November 2003, Pages 232-242
Methods

Immunization with DNA through the skin

https://doi.org/10.1016/S1046-2023(03)00137-3Get rights and content

Abstract

The skin has evolved as a barrier to prevent external agents, including pathogens, from entering the body. It has a complex and efficient immune surveillance system, which includes Langerhans cells and dendritic cells. By targeting the body’s natural defense system, skin–DNA immunization attempts to produce an efficient immune response. Nucleic acid vaccines provide DNA for protein expression in a variety of cells, including keratinocytes, Langerhans cells, and dendritic cells, which are located in the two main areas of the skin, the epidermis (the most superficial layer) and the dermis. After maturation, Langerhans cells and dermal dendritic cells can migrate to local lymph nodes where presentation of antigens to T cells can occur and thus start a variety of immunologic responses. Dermal immunization methods described in this article target the epidermis, the dermis, or both and include: (a) stripping; (b) chemical modification; (c) trans-epidermal immunization (transcutaneous immunization or non-invasive vaccination of the skin); (d) gene gun technology; (e) electroporation; (f) intradermal injections; and (g) microseeding. These techniques all require the removal of hair, the circumvention or modification of the stratum corneum layer of the epidermis, and the addition of DNA or amplification of DNA signal. As the biology of the skin and the mechanisms of DNA vaccination are elucidated, these skin immunization techniques will be optimized. With refinement, skin–DNA immunization will achieve the goal of producing a reliable and efficacious immune response to a variety of pathogens.

Introduction

The skin is divided into two main layers, the epidermis and the dermis (Fig. 1). The epidermis acts as a physical barrier, the first line of immune surveillance, and is responsible for prevention of desiccation and mechanical agitation. The second layer, the dermis, is responsible for blood supply to the epidermis, thermoregulation, and also immune surveillance. The epidermis makes up the most superficial layer of the skin. Within the epidermis, the stratum corneum is the outermost layer, which consists mainly of keratin and thus acts as a barrier. In the stratum granuloma, a deeper layer of the epidermis, there is a hydrophobic layer made up of various lipids that are important in the retention of water. The lipids also have bacterial and fungal static properties and may also serve a role in keeping external compounds from entering the deeper layers of the skin [1].

The skin has evolved as a barrier to shield external agents, including pathogens, from entering the body. By targeting the body’s natural defense system, the skin, dermal DNA immunization attempts to produce an immunologically efficacious response. DNA vaccines provide DNA for protein expression in a variety of cells, including keratinocytes, Langerhans cells (LHC), and dendritic cells (DC), which are located in the two main areas of the skin, the epidermis (the most superficial layer) and the dermis (Fig. 1). After maturation, the LHC, which are found mainly in the epidermis, and the dermal DC, which are found mainly in the dermis, can migrate to local lymph nodes where presentation of antigens to T cells can occur and initiate a variety of immunological responses [2].

Section snippets

Techniques for DNA skin immunization

Each of the techniques described can be categorized into three groups, depending on which stratum of the skin is targeted (Fig. 2). The first group encompasses epidermal immunization, which includes stripping, chemical modification, and trans-epidermal immunization (transcutaneous immunization [TCI]/non-invasive vaccination by skin [NIVS]). The second group covers epidermal and dermal immunization, which includes gene gun technology and electroporation. The third group targets dermal

Questions and areas of optimization for skin–DNA immunization

DNA immunization via the skin holds great potential. However, there are multiple areas for optimization. Questions addressing skin physiology, assay development, immune response amplification, and translational applications remain to be answered.

Physiologically, the area of the skin that is best for immunization, whether the abdomen, a limb, the back, or an ear, is still unresolved [56]. The depth of skin immunization, and therefore the best skin layer to immunize, whether it is the dermis, the

Summary

As the biology of the skin and the mechanisms of DNA vaccination are elucidated, optimization of these skin techniques should become more refined. With refinement, skin–DNA immunization will achieve the goal of producing a reproducible and efficacious immune response to a variety of pathogens.

References (61)

  • Z Shi et al.

    Vaccine

    (1999)
  • B Lu et al.

    J. Invest. Dermatol.

    (1997)
  • T Scharton-Kersten et al.

    Vaccine

    (1999)
  • L VanderZanden et al.

    Virology

    (1998)
  • J.W Hooper et al.

    Virology

    (1999)
  • D Chen et al.

    Vaccine

    (2001)
  • M.A Barry et al.

    Vaccine

    (1997)
  • H Tighe et al.

    Immunol. Today

    (1998)
  • M.A Liu et al.

    Mol. Ther.

    (2000)
  • L Zhang et al.

    Biochem. Biophys. Acta

    (2002)
  • J.J Drabick et al.

    Mol. Ther.

    (2001)
  • J Glasspool-Malone et al.

    Mol. Ther.

    (2000)
  • R Heller et al.

    FEBS Lett.

    (1996)
  • C Watkins et al.

    Vet. Immunol. Immunopathol.

    (1999)
  • K Yamakami et al.

    Parasitol. Int.

    (2001)
  • E Eriksson et al.

    J. Surg. Res.

    (1998)
  • L Dupre et al.

    Vaccine

    (2001)
  • D.P Lunn et al.

    Vaccine

    (1999)
  • C.C Norbury et al.

    Nat. Immunol.

    (2002)
  • E Raz et al.

    Proc. Natl. Acad. Sci. USA

    (1994)
  • L.J Lui et al.

    Vaccine

    (2001)
  • L Li et al.

    Nat. Med.

    (1995)
  • M.Y Alexander et al.

    Hum. Mol. Genet.

    (1995)
  • F.J Forster et al.

    Arch. Dermatol. Res.

    (1975)
  • R Ogura et al.

    Arch. Dermatol. Res.

    (1983)
  • G.M Glenn et al.

    Nature

    (1998)
  • S.A Hammond et al.

    Crit. Rev. Ther. Drug Carrier Syst.

    (2001)
  • M Sedegah et al.

    Proc. Natl. Acad. Sci. USA

    (1994)
  • Z Shi et al.

    J. Virol.

    (2001)
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