Transcutaneous immunization: A human vaccine delivery strategy using a patch

Glenn, Gregory M.; Taylor, David N.; Li, Xiuru; Frankel, Sarah S.; Montemarano, Andrew D.; Alving, Carl R.

doi:10.1038/82225

Cited by 313 publications

(191 citation statements)

References 19 publications

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“…There is significant interest in developing epicutaneous vaccination because of the potential for self-administration, ease of delivery and stockpiling, and lack of systemic side effects (26,27). This strategy, delivery of a protein Ag after skin hydration or mild abrasion, has been shown to be effective for multiples Ags and provides protective immunity against virus infection (28,29).…”

Section: A Limited Immune-promoting Role For Langerin ϩ Cellsmentioning

confidence: 99%

Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions

Wang

Bursch

Kissenpfennig

et al. 2008

The Journal of Immunology

106

102

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There are conflicting data in the literature regarding the role of epidermal Langerhans cells (LC) in promoting skin immune responses. On one hand, LC can be extremely potent APCs in vitro, and are thought to be involved in contact hypersensitivity (CHS). On the other hand, it seems counterintuitive that a cell type continually exposed to pathogens at the organism’s barrier surfaces should readily trigger potent T cell responses. Indeed, LC depletion in one model led to enhanced contact hypersensitivity, suggesting they play a negative regulatory role. However, apparently similar LC depletion models did not show enhanced CHS, and in one case showed reduced CHS. In this study we found that acute depletion of mouse LC reduced CHS, but the timing of toxin administration was critical: toxin administration 3 days before priming did not impair CHS, whereas toxin administration 1 day before priming did. We also show that LC elimination reduced the T cell response to epicutaneous immunization with OVA protein Ag. However, this reduction was only observed when OVA was applied on the flank skin, and not on the ear. Additionally, peptide immunization was not blocked by depletion, regardless of the site. Finally we show that conditions which eliminate epidermal LC but spare other Langerin+ DC do not impair the epicutaneous immunization response to OVA. Overall, our results reconcile previous conflicting data in the literature, and suggest that Langerin+ cells do promote T cell responses to skin Ags, but only under defined conditions.

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Section: A Limited Immune-promoting Role For Langerin ϩ Cellsmentioning

confidence: 99%

Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions

Wang

Bursch

Kissenpfennig

et al. 2008

The Journal of Immunology

106

102

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“…Transcutaneous immunization by topical administration of CT to the skin has been demonstrated to induce a systemic antibody response against both itself and co-administered proteins in mice [74], humans [76], sheep, cats and dogs [81]. In mice [75] and humans [76] it was shown that this immunization route also induces a mucosal immune response.…”

Section: Cholera Toxinmentioning

confidence: 99%

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

et al. 2006

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-In developing veterinary mucosal vaccines and vaccination strategies, mucosal adjuvants are one of the key players for inducing protective immune responses. Most of the mucosal adjuvants seem to exert their effect via binding to a receptor/or target cells and these properties were used to classify the mucosal adjuvants reviewed in the present paper: (1) ganglioside receptor-binding toxins (cholera toxin, LT enterotoxin, their B subunits and mutants); (2) surface immunoglobulin binding complex CTA1-DD; (3) TLR4 binding lipopolysaccharide; (4) TLR2-binding muramyl dipeptide; (5) Mannose receptor-binding mannan; (6) Dectin-1-binding ß 1,3/1,6 glucans; (7) TLR9-binding CpG-oligodeoxynucleotides; (8) Cytokines and chemokines; (9) Antigen-presenting cell targeting ISCOMATRIX and ISCOM. In addition, attention is given to two adjuvants able to prime the mucosal immune system following a systemic immunization, namely 1α, 25(OH) 2 D 3 and cholera toxin.

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“…Using a simple patch/skin-hydration approach, Glenn et al have demonstrated that effective immunity against protein antigens can be elicited by formulating the vaccine with a bacterial toxin. 26,27 Whether or not the hydration technology will influence genetic vaccines remains to be determined. Gene-gun delivery, which requires that the vaccine inoculum be precipitated onto gold beads, was initially thought to be restricted to plasmid vaccines due to formulation issues.…”

Section: Discussionmentioning

confidence: 99%

Enabling topical immunization via microporation: a novel method for pain-free and needle-free delivery of adenovirus-based vaccines

et al. 2003

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The skin represents an excellent site for vaccine inoculation due to its natural role as a first line of contact with foreign pathogens and the high local frequency of antigen presenting cells. To facilitate skin-directed immunization, a new technique has been developed (termed microporation) whereby a vaporization process is used to remove tiny areas of the stratum corneum creating microscopic pores that allow access to the underlying viable epidermis. Reporter gene expression was 100-fold increased following application of an adenovirus vector to microporated skin when compared to intact skin. Furthermore, 10-100-fold greater cellular and humoral immune responses were observed following topical administration of an adenovirus vaccine to microporated skin versus intact skin. Hairless mice responded to the microporated adenovirus vaccine equivalently to mice with normal hair follicle distribution demonstrating the activity of the microporated vaccine was not related to follicle count. In a tumor challenge model using a surrogate antigen, microporation increased vaccine efficacy by approximately 100-fold compared to intact skin. Finally, microporation enabled delivery of an adenovirus vaccine carrying a relevant melanoma antigen resulting in the development of autoimmune vitiligo and tumor protection. Thus, the microporation technology has proven to be a reliable and easy method to enable skin-directed vaccination.

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Transcutaneous immunization: A human vaccine delivery strategy using a patch

Cited by 313 publications

References 19 publications

Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions

Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

Enabling topical immunization via microporation: a novel method for pain-free and needle-free delivery of adenovirus-based vaccines

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