Current Opportunities and Challenges in Intradermal Vaccination

Chen, David; Bowersock, T. L.; Weeratna, Risini D.; Yeoh, Thean

doi:10.4155/tde.15.65

Cited by 14 publications

(9 citation statements)

References 30 publications

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“…The ID route is particularly interesting to get patients' compliance due to the easy accessibility to the skin [28]. A number of strategies have been proposed for the ID delivery of antigens without the employment of needles, such as high-velocity needle-free injection systems, permeability enhancers to disrupt the stratum corneum, or the use of antigen delivery systems with percutaneous absorption properties or diffusive capacity [29].…”

Section: Discussionmentioning

confidence: 99%

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

et al. 2019

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Intradermal (ID) immunization is of increasing interest due to the easy accessibility and excellent immunogenic properties of the skin. Among ID immunization methods, dissolving microneedles (MNs) have appeared as an alternative to traditional hypodermic immunization, offering many advantages, such as being an easily administered method, with no need for health personnel, painless, and avoiding the use of needles and sharp wastage. In this study, an affordable and easy-to-produce MNs method was developed based on aqueous blends of 30% w/w poly (methyl vinyl ether-co-maleic anhydride). As an antigen model, a subunit vaccine candidate based on outer membrane vesicles from Shigella flexneri was used. Both unloaded and antigen-loaded MNs were synthetized and characterized. The MNs were successfully validated in an in vitro Parafilm M ® skin model and in a pig skin ex vivo model. Biodistribution studies were performed in BALB/c mice using 99m TcO 4 − radiolabeled samples. Results indicated that the vesicle vaccine was successfully released from the MNs and targeted gastrointestinal tract after 6 h post-administration. In vivo immunization and protection studies were performed in BALB/c mice. Mice were intradermally immunized through ear skin with one single dose of 200 µg antigenic complex, eliciting the production of specific systemic IgG and mucosal IgA. Moreover, MNs were able to protect mice from an experimental infection with 1×10 6 CFU/mouse of S. flexneri four weeks after immunization. This work demonstrates for the first time the potential of outer membrane vesicle-loaded dissolving MNs for ID vaccination against enteropathogens like Shigella.Vaccines 2019, 7, 159 2 of 15 (SALT), formed by a great network of immune cells, including Langerhans cells (LC), lymphocytes, and dendritic cells (DCs), which recognize the antigens and present them in the proximal lymph nodes [3]. Different ID vaccination methods have been used already, such as the Mantoux technique, microinjection systems, or jet injectors, used for smallpox, rabies, or Bacillus Calmette-Guérin (BCG) vaccines. However, they require the use of needles [4]. Microneedle patches (MNs) have appeared as a novel and attractive approach for ID immunization [5]. They are painless devices formed by arrays of micron-size projections that can pass through the stratum corneum and epidermis without reaching the nerves of the dermis layer [6]. Thus, they are a self-administered, minimally invasive method, well tolerated by human patients in proof of concept trials [7,8], that can directly target the skin immune cells [9].Several types of MNs have been developed for the delivery of antigens: solid, coated, hollow, and dissolving MNs [10]. Among them, and based on their self-disabling properties, dissolving MNs (MNs) have been selected for this work. These MNs are made of a soluble matrix, generally a biocompatible polymer or polysaccharide, which includes the antigenic complex. After the array insertion into the skin, the needle tips dissolve and the antigenic cargo i...

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Section: Discussionmentioning

confidence: 99%

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

et al. 2019

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“…ID vaccines are comparable and in some cases superior to IM vaccines in terms of immunogenicity, safety, reactogenicity, tolerability and cross-protection profiles, as well as in terms of patient preference, acceptance and vaccine selection. [103][104][105][106][107][108] Further advances, such as Fluzone® ID with alternative B strains and Quadrivalent Fluzone® ID or the possibility of self-administering the vaccines, make Fluzone® ID and Intanza® even more valuable. …”

Section: Resultsmentioning

confidence: 99%

Fluzone® intra-dermal (Intanza®/Istivac® Intra-dermal): An updated overview

Bragazzi

Orsi

Ansaldi

et al. 2016

Human Vaccines & Immunotherapeutics

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Influenza is a highly contagious respiratory acute viral disease which imposes a very heavy burden both in terms of epidemiology and costs, in the developed countries as well as in the developing ones. It represents a serious public health concern and vaccination constitutes an important tool to reduce or at least mitigate its burden. Despite the existence of a broad armamentarium against influenza and despite all the efforts and recommendations of international organisms to broaden immunization, influenza vaccination coverage is still far from being optimal. This, taken together with logistic and technical difficulties that can result into vaccine shortage, makes intra-dermal (ID) vaccines, such as Fluzone® ID and Intanza®, particularly attractive. ID vaccines are comparable and, in some cases, superior to intra-muscular/sub-cutaneous vaccines in terms of immunogenicity, safety, reactogenicity, tolerability and cross-protection profiles, as well as in terms of patient preference, acceptance and vaccine selection. Further advances, such as Fluzone® ID with alternative B strains and Quadrivalent Fluzone® ID or the possibility of self-administering the vaccines, make influenza ID vaccines even more valuable.

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“…The local skin environment facilitates optimal migration to the draining lymphoid organs and control of the immune response. This is supported by skin based vaccination strategies that in humans resulted in highly efficient immunization 38 . Interesting in this respect are intradermal dendritic cell (DC) vaccination trials that resulted in superior antitumor T-cell induction and faster transit to draining LN 39 – 42 .…”

Section: Discussionmentioning

confidence: 99%

Intradermal injection of low dose human regulatory T cells inhibits skin inflammation in a humanized mouse model

Landman

Oliveira

Erp

et al. 2018

Sci Rep

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Recent regulatory T cell (Treg) based clinical trials support their therapeutic potential in transplantation and auto-inflammatory diseases. However, large numbers of Treg are needed to accomplish therapeutic efficacy. Local injection at the site of inflammation (targeted delivery) may lower the numbers needed for therapy. We evaluated if local delivery of low numbers of human Treg by intradermal injection was able to prevent skin inflammation, using the humanized mouse huPBL-SCID-huSkin allograft model. A dose of only 1 × 105 freshly isolated, non expanded Treg injected intradermally in close proximity to the transplanted human skin prevented inflammation of the grafted tissue induced by 4 × 107 IP injected human allogeneic PBMCs, (ratio Treg:PBMC = 1:400), as indicated by the inhibition of epidermal thickening, sustained Keratin-10 expression, the absence of Keratin-16 up regulation and prevention of human CD3+ T cell influx. A concomitant reduction of human T cells was observed in lymph nodes and spleen of the mice. Injection of Treg at the contralateral side was also shown to inhibit skin inflammation, suggesting that the inflammatory response was regulated both locally and systemically. In conclusion, local application of Treg may be an attractive way to suppress inflammation in vivo without the need for prior ex vivo expansion.

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Current Opportunities and Challenges in Intradermal Vaccination

Cited by 14 publications

References 30 publications

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

Dissolving Microneedles for Intradermal Vaccination against Shigellosis

Fluzone® intra-dermal (Intanza®/Istivac® Intra-dermal): An updated overview

Intradermal injection of low dose human regulatory T cells inhibits skin inflammation in a humanized mouse model

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