Microneedle‐based intradermal delivery of stabilized dengue virus

Turvey, Michelle E.; Uppu, Divakara S. S. M.; Sharif, Abdul Rahim Mohamed; Bidet, Katell; Alonso, Sylvie; Ooi, Eng Eong; Hammond, Paula T.

doi:10.1002/btm2.10127

Cited by 27 publications

(18 citation statements)

References 77 publications

(137 reference statements)

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“…Dissolvable/biodegradable MAP types have been tested pre-clinically for intracutaneous vaccination against a wide range of viral infections, such as influenza, hepatitis B, HIV, measles, rubella, rabies, polio, dengue, Ebola, Zika, hepatitis C, rotavirus, MERS, and COVID-19, with several types of antigen platforms, including subunit, nucleic acid, VLPs, recombinant viral vector, live attenuated viruses, and inactivated viruses [ 198 , [311] , [312] , [313] , [314] , [315] , [316] , [317] , [318] , [319] , [320] , [321] , [322] , [323] , [324] , [325] , [326] , [327] , [328] , [329] , [330] , [331] , [332] , [333] , [334] , [335] , [336] ]. These studies have utilized various animal models, such as mouse, rhesus macaque, dog, pig, and guinea pig [ 316 , 321 , 328 , 333 , 337 ].…”

Section: Microarray Patchesmentioning

confidence: 99%

Microarray patches enable the development of skin-targeted vaccines against COVID-19

Korkmaz

Balmert

Sumpter

et al. 2021

Advanced Drug Delivery Reviews

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The COVID-19 pandemic is a serious threat to global health and the global economy. The ongoing race to develop a safe and efficacious vaccine to prevent infection by SARS-CoV-2, the causative agent for COVID-19, highlights the importance of vaccination to combat infectious pathogens. The highly accessible cutaneous microenvironment is an ideal target for vaccination since the skin harbors a high density of antigen-presenting cells and immune accessory cells with broad innate immune functions. Microarray patches (MAPs) are an attractive intracutaneous biocargo delivery system that enables safe, reproducible, and controlled administration of vaccine components (antigens, with or without adjuvants) to defined skin microenvironments. This review describes the structure of the SARS-CoV-2 virus and relevant antigenic targets for vaccination, summarizes key concepts of skin immunobiology in the context of prophylactic immunization, and presents an overview of MAP-mediated cutaneous vaccine delivery. Concluding remarks on MAP-based skin immunization are provided to contribute to the rational development of safe and effective MAP-delivered vaccines against emerging infectious diseases, including COVID-19.

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Section: Microarray Patchesmentioning

confidence: 99%

Microarray patches enable the development of skin-targeted vaccines against COVID-19

Korkmaz

Balmert

Sumpter

et al. 2021

Advanced Drug Delivery Reviews

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show abstract

“…Coated MNs are a sub-category of MNs that facilitate intradermal delivery of therapeutics by dissolution of the coating formulation within the local biological environment following their application to the skin surface (Prausnitz 2017). This MN sub-type targets LCs and dDCs (Turvey et al 2019) but minimizes damage to the local tissue and therefore may be particularly useful in the clinical context of ASI.…”

Section: Introductionmentioning

confidence: 99%

Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes

Arikat

Hanna

Singh

et al. 2020

Journal of Controlled Release

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Antigen-specific immunotherapy (ASI) has been proposed as an alternative treatment strategy for type 1 diabetes (T1D). ASI aims to induce a regulatory, rather than stimulatory, immune response in order to reduce, or prevent, autoimmune mediated β-cell destruction, thus preserving endogenous insulin production. The abundance of immunocompetent antigen presenting cells (APCs) within the skin makes this organ an attractive target for immunotherapies. Microneedles (MNs) have been proposed as a suitable drug delivery system to facilitate intradermal delivery of autoantigens in a minimally invasive manner. However, studies to date have employed single peptide autoantigens, which would restrict ASI to patients expressing specific Human Leukocyte Antigen (HLA) molecules, thus stratifying the patient population. This study aims to develop, for the first time, an intradermal MN delivery system to target proinsulin, a large multi-epitope protein capable of inducing tolerance in a heterogenous (in terms of HLA status) population of T1D patients, to the immunocompetent cells of the skin. An optimized three component coating formulation containing proinsulin, a diluent and a surfactant, facilitated uniform and reproducible coating of >30μg of the active pharmaceutical ingredient on a stainless steel MN array consisting of thirty 500μm projections. When applied to a murine 2 model these proinsulin-coated MNs efficiently punctured the skin and after a limited insertion time (150 seconds) a significant proportion of the therapeutic payload (86%) was reproducibly delivered into the local tissue. Localized delivery of proinsulin in non-obese diabetic (NOD) mice using the coated MN system stimulated significantly greater proliferation of adoptively transferred antigen-specific CD8+ T cells in the skin draining lymph nodes compared to a conventional intradermal injection. This provides evidence of targeted delivery of the multi-epitope proinsulin antigen to skinresident APCs, in vivo, in a form that enables antigen presentation to antigen-specific T cells in the local lymph nodes. The development of an innovative coated MN system for highly targeted and reproducible delivery of proinsulin to local immune cells warrants further evaluation to determine translation to a tolerogenic clinical outcome.

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“…Similarly, preclinical studies based on inactivated or subunit DENV vaccines showed that the i.d. delivery route increases the number of DCs at the inoculation site, the generation of neutralizing antibody titers, and CD8+ T cells compared to the effects after other immunization routes [ 24 , 25 , 26 , 27 , 28 ]. Moreover, the i.d.…”

Section: Introductionmentioning

confidence: 99%

Intradermal Delivery of Dendritic Cell-Targeting Chimeric mAbs Genetically Fused to Type 2 Dengue Virus Nonstructural Protein 1

et al. 2020

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Targeting dendritic cells (DCs) by means of monoclonal antibodies (mAbs) capable of binding their surface receptors (DEC205 and DCIR2) has previously been shown to enhance the immunogenicity of genetically fused antigens. This approach has been repeatedly demonstrated to enhance the induced immune responses to passenger antigens and thus represents a promising therapeutic and/or prophylactic strategy against different infectious diseases. Additionally, under experimental conditions, chimeric αDEC205 or αDCIR2 mAbs are usually administered via an intraperitoneal (i.p.) route, which is not reproducible in clinical settings. In this study, we characterized the delivery of chimeric αDEC205 or αDCIR2 mAbs via an intradermal (i.d.) route, compared the elicited humoral immune responses, and evaluated the safety of this potential immunization strategy under preclinical conditions. As a model antigen, we used type 2 dengue virus (DENV2) nonstructural protein 1 (NS1). The results show that the administration of chimeric DC-targeting mAbs via the i.d. route induced humoral immune responses to the passenger antigen equivalent or superior to those elicited by i.p. immunization with no toxic effects to the animals. Collectively, these results clearly indicate that i.d. administration of DC-targeting chimeric mAbs presents promising approaches for the development of subunit vaccines, particularly against DENV and other flaviviruses.

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Microneedle‐based intradermal delivery of stabilized dengue virus

Cited by 27 publications

References 77 publications

Microarray patches enable the development of skin-targeted vaccines against COVID-19

Microarray patches enable the development of skin-targeted vaccines against COVID-19

Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes

Intradermal Delivery of Dendritic Cell-Targeting Chimeric mAbs Genetically Fused to Type 2 Dengue Virus Nonstructural Protein 1

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