Immunity under the skin: potential application for topical delivery of vaccines

Partidos, Charalambos D.; Beignon, Anne-Sophie; Mawas, Fatme; Belliard, Guillaume; Briand, Jean‐Paul; Muller, Sylviane

doi:10.1016/s0264-410x(02)00597-2

Cited by 49 publications

(36 citation statements)

References 15 publications

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“…Although we did not characterize the type of anti-sTat T cell response phenotypically, it is likely that transcutaneous immunization elicited both CD4 + and CD8 + sTat-specific T cells. This assumption is based on published work demonstrating the capacity of ADP-ribosylating exotoxins to promote the induction of both T helper [16] and cytotoxic T cell responses [18,31,36] after transcutaneous immunization. Furthermore, splenocytes of mice immunized with sTat + CT secreted IFN-c and IL-6 upon in vitro restimulation with sTat or peptide 44-61.…”

Section: Discussionmentioning

confidence: 99%

“…It is composed of 86-101 amino acid residues (depending on the isolate) encoded by two exons. The first 72 amino acid residues (encoded by the first exon) are organized into three functional domains: (i) an acidic N-terminal region (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] that binds to cell surface CD26 and is thought to mediate immunosuppressive activity [3]; (ii) a cysteine-rich domain (aa [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] that mediates binding to chemokine receptors [4]; and (iii) the basic domain (aa 41-60). The latter domain is responsible for the internalization of extracellular Tat and its import into the nucleus and is also required for binding to short RNA transcripts containing the viral transactivation-responsive element (TAR) [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Transcutaneous immunization is based on the co-application of antigen with an ADPribosylating exotoxin, such as cholera toxin (CT) secreted by Vibrio cholerae [11], heat-labile enterotoxin of Escherichia coli (LT) [14,15] or mutants of LT [14,16,17] onto hydrated bare skin. Studies in mice have shown that transcutaneous immunization elicits systemic and mucosal immune responses to various types of antigens including proteins, peptides, glycoconjugate vaccines, viruses and plasmid DNA [18], and its potential was more recently shown in humans [19,20].…”

Section: Introductionmentioning

confidence: 99%

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A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

et al. 2004

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The HIV‐1 Tat protein plays a critical role in the pathogenesis of HIV and has been considered as a candidate vaccine antigen. In an effort to design a non‐invasive vaccination strategy against HIV‐1 that stimulates the induction of systemic and mucosal immune responses, we studied the transcutaneous delivery of a synthetic Tat protein using cholera toxin as an adjuvant. Following immunization of BALB/c mice with various doses of Tat, IgG and IgA antibody responses were measured in the serum and vaginal washes, respectively. Serum antibodies predominantly recognized the N‐terminal and basic functional domains of the protein and exhibited neutralizing capacity against Tat‐driven transactivation. Transcutaneous immunization also elicited potent cellular immune responses against Tat and the secretion of high levels of IL‐2, IFN‐γ and IL‐6. These findings demonstrate for the first time that by using a simple and safe immunization procedure, a synthetic Tat protein can elicit potentially protective immune responses. Transcutaneous immunization may be advantageous for the non‐invasive delivery of other HIV candidate vaccine antigens.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

et al. 2004

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“…Immunization strategies through the skin have proven to be feasible and elicit both systemic and mucosal immunity (4,5). In murine studies, CD4 ϩ and CD8 ϩ T cell responses were both observed after peptide immunization through the skin (6,7).…”

Section: Accination With Dendritic Cells (Dc)mentioning

confidence: 99%

Tumor Immunotherapy by Epicutaneous Immunization Requires Langerhans Cells

Stoitzner

Green

Jung

et al. 2008

The Journal of Immunology

103

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A role for Langerhans cells (LC) in the induction of immune responses in the skin has yet to be conclusively demonstrated. We used skin immunization with OVA protein to induce immune responses against OVA-expressing melanoma cells. Mice injected with OVA-specific CD8+ T cells and immunized with OVA onto barrier-disrupted skin had increased numbers of CD8+ T cells in the blood that produced IFN-γ and killed target cells. These mice generated accelerated cytotoxic responses after secondary immunization with OVA. Prophylactic or therapeutic immunization with OVA onto barrier-disrupted skin inhibited the growth of B16.OVA tumors. LC played a critical role in the immunization process because depletion of LC at the time of skin immunization dramatically reduced the tumor-protective effect. The topically applied Ag was presented by skin-derived LC in draining lymph nodes to CD8+ T cells. Thus, targeting of tumor Ags to LC in vivo is an effective strategy for tumor immunotherapy.

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“…In addition, systemic delivery via the skin using transdermal patches has also been highly successful [1]. Finally, there is growing interest to deliver vaccines to the skin for a more potent immune response [2] Progress on these applications is severely limited by the strong barrier properties of the skin imposed primarily by the outer layer of stratum corneum, which measures just 10-20 μm in thickness, but permits transport only of low doses of small, lipophilic molecules [1]. Although a small number of drugs with suitable characteristics can be delivered across stratum corneum and into the skin at therapeutic levels, there has been intensive research to develop ways to increase skin permeability and to deliver larger quantities, especially of large, hydrophilic compounds like peptides and proteins.…”

Section: Introductionmentioning

confidence: 99%

Pocketed microneedles for drug delivery to the skin

Gill¹,

Prausnitz²

2008

Journal of Physics and Chemistry of Solids

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Drug delivery to the skin is limited by the strong barrier properties of skin's outer layer of stratum corneum. Micron-scale needles have been developed to deliver drugs across this barrier layer and into the skin in a minimally invasive manner. One method of delivery involves coating these microneedles with a drug that rapidly dissolves off within the skin. As a variation on this approach, this study examines microneedles with holes cut through their shafts to form "pockets" that can be filled with drug formulations using a dip-coating method. Our results (i) demonstrated the filling of microneedle pockets having a variety of different sizes and shapes, (ii) quantified the amount of drug that can be filled into pockets and coated onto microneedle surfaces, (iii) developed composite microneedle structures that sequester one model drug within the microneedle pocket and coat another model drug on the microneedle surface and (iv) showed that pocketed microneedles can deliver a model drug to a targeted depth within the skin. We conclude that pocketed microneedles offer unique capabilities for controlled drug delivery to the skin.

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Immunity under the skin: potential application for topical delivery of vaccines

Cited by 49 publications

References 15 publications

A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

Tumor Immunotherapy by Epicutaneous Immunization Requires Langerhans Cells

Pocketed microneedles for drug delivery to the skin

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