Emerging skin-targeted drug delivery strategies to engineer immunity: A focus on infectious diseases

Korkmaz, Emrullah; Balmert, Stephen C.; Carey, Cara Donahue; Erdö́s, G.; Falo, Louis D.

doi:10.1080/17425247.2021.1823964

Cited by 17 publications

(16 citation statements)

References 267 publications

(272 reference statements)

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“…Although the role of skin as a protective physical barrier has been broadly recognized, its unique ability to serve as an immune-responsive organ has more recently been appreciated due to advances in our understanding of skin immune mechanisms that initiate and regulate innate and adaptive immune responses against invading pathogens [ [89] , [90] , [91] , [92] ]. Emerging knowledge has revealed that there is both a high density of professional antigen-presenting cells (APCs) and immune-accessory cells that form a tightly regulated immune network within the skin microenvironment [ 42 , [91] , [92] , [93] , [94] , [95] , [96] ]. Our increasing understanding of the mechanisms underlying immune regulation in the skin provides novel opportunities to rationally develop effective skin-targeted vaccines based on localized immune engineering.…”

Section: The Skin As An Immune-responsive Organmentioning

confidence: 99%

“…Microarray patches (MAPs) are among the most promising skin-targeted vaccine delivery systems [ 42 , 44 , 202 ]. One of the major roadblocks to the success of intracutaneous immunization has been the lack of safe, effective, convenient, patient-friendly, and inexpensive delivery technologies that can reliably administer vaccines to targeted skin microenvironments [ 167 , 170 , 203 ].…”

Section: Microarray Patchesmentioning

confidence: 99%

“…To obviate these challenges, innovative vaccine delivery technologies are being developed, which may be particularly relevant for emerging pandemics [ [37] , [38] , [39] , [40] , [41] ]. Microarray patches (MAPs) are among the most attractive vaccine delivery systems and offer unique advantages that could improve the safety, compliance, coverage, immunogenicity, and cost of immunization by targeting vaccine components to cutaneous microenvironments [ 42 ]. Skin-targeted vaccines have the potential to be more immunogenic due to the immune-responsive nature of the skin compared to subcutaneous or intramuscular tissues targeted by prevailing vaccination routes [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

“…Microarray patches (MAPs) are among the most attractive vaccine delivery systems and offer unique advantages that could improve the safety, compliance, coverage, immunogenicity, and cost of immunization by targeting vaccine components to cutaneous microenvironments [ 42 ]. Skin-targeted vaccines have the potential to be more immunogenic due to the immune-responsive nature of the skin compared to subcutaneous or intramuscular tissues targeted by prevailing vaccination routes [ 42 ]. These advantages, and the potential to obviate the cold-chain by stabilizing vaccine components in the delivery device, could enable minimally invasive delivery, self-administration, and economically advantageous refrigeration-free storage and distribution [ [42] , [43] , [44] , [45] , [46] ].…”

Section: Introductionmentioning

confidence: 99%

“…Skin-targeted vaccines have the potential to be more immunogenic due to the immune-responsive nature of the skin compared to subcutaneous or intramuscular tissues targeted by prevailing vaccination routes [ 42 ]. These advantages, and the potential to obviate the cold-chain by stabilizing vaccine components in the delivery device, could enable minimally invasive delivery, self-administration, and economically advantageous refrigeration-free storage and distribution [ [42] , [43] , [44] , [45] , [46] ]. As such, skin-targeted vaccination using MAPs has received considerable attention, including recent efforts to develop MAP-delivered coronaviruses vaccines.…”

Section: Introductionmentioning

confidence: 99%

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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: The Skin As An Immune-responsive Organmentioning

confidence: 99%

Section: Microarray Patchesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Korkmaz

Balmert

Sumpter

et al. 2021

Advanced Drug Delivery Reviews

Self Cite

View full text Add to dashboard Cite

show abstract

Advanced Materials for SARS‐CoV‐2 Vaccines

et al. 2022

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development, since it mediates viral entry and induces neutralizing antibody responses, which are predictive of protection from symptomatic SARS-CoV-2 infection. [2,3] As waves of new viral variants emerge, other targets such as the membrane (M), envelope (E), or nucleocapsid (N) proteins may emerge as complementary vaccine antigens to help increase breadth of protection. [4] S forms a homotrimeric structure comprising two domains, S1 and S2, separated by a Furin cleavage site (FCS). [5,6] S1 contains the receptor binding domain (RBD) which binds to human angiotensin converting enzyme 2 (hACE2) on host cells. Subsequently, proteolytic cleavage by Furin and by Transmembrane protease serine 2 (TMPRSS2) at the FCS and just upstream of the fusion peptide, respectively, activates the S2 fusion machinery leading to viral entry. [7] S is a class I fusion glycoprotein that undergoes major structural rearrangements from prefusion to post-fusion conformation during viral fusion to host cell membranes. It was previously shown that prefusion-stabilized class I fusion protein antigens better preserve neutralization epitopes for viruses including respiratory syncytial virus (RSV) fusion (F) glycoprotein. [8] Similar to the Middle East respiratory syndrome coronavirus (MERS-CoV) S protein, [9] two proline substitutions (2P) at residues 986 and 987 at the C-terminal boundary of the first heptad repeat were found to stabilize SARS-CoV-2 S in its prefusion conformation. [10] These 2P stabilizing mutations have been widely adopted in many SARS-CoV-2 vaccines including the Moderna mRNA-1273 vaccine (Spikevax), the Pfizer/BioNTech BNT162b2 vaccine (Comirnaty), the Novavax NVX-CoV2373 vaccine (Nuvaxovid), and the Johnson and Johnson Ad26.CoV2.S vaccine (Janssen COVID-19 Vaccine). [11] In contrast, the AstraZeneca/Oxford ChAdOx1 nCoV-19/AZD1222 (Vaxzevria) antigen uses the wildtype SARS-CoV-2 S sequence and cells transduced with the adenovirusvectored vaccine produce intact trimeric S, albeit with some proteolytic S degradation. [12] To mitigate this, another common antigen enhancement strategy used by NVX-CoV2373 [13] and Ad26.CoV2.S [14] for example, is to insert mutations or deletions at the proteolytic-prone FCS to improve antigen stability and preserve immunogenicity.As shown in the schematic illustration in Figure 1B, COVID-19 vaccines have taken on a wide variety of formats. Table 1 lists some of the vaccine types that have reported peerreviewed phase 3 clinical trial results so far. [16] Various advanced materials have emerged as vaccines for the S subunit antigen The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has killed untold millions worldwide and has hurtled vaccines into the spotlight as a go-to approach to mitigate it. Advances in virology, genomics, structural biology, and vaccine technologies have enabled a rapid and unprecedented rollout of COVID-19 vaccines, although much of the developing world remains unvaccinated. Several new vaccine platform...

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