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

Abstract

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.

Keywords: COVID-19; Cutaneous immunobiology; Infectious diseases; Microarray patches; Prophylactic immunization; SARS-CoV-2; Skin-targeted vaccines; Spike protein.

Graphical abstract

Fig. 1

Structural properties of the enveloped, positive-sense, single-stranded RNA virus SARS-CoV-2 and mechanism of SARS-CoV-2 entry into host cells. Critical viral components include Envelope (E), Membrane (M), Nucleocapsid (N), and Spike (S) proteins. The S protein consists of two subunits (S1 and S2) and plays a major role in the infection of host cells, as the receptor-binding domain (RBD) of the S protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor on host cells.

Fig. 2

The skin is a vital protective barrier against environmental threats, and an active immunological site that harbors professional antigen-presenting cells and diverse immune accessory cells that regulate cutaneous immune mechanisms and initiate and modulate adaptive immune responses to invading pathogens and skin-delivered vaccine components.

Fig. 3

Skin vaccination induces antigen-specific cellular and humoral immune responses. Introduction of vaccine components into the skin microenvironment results in antigen loading and functional skewing of skin-resident APCs capable of directly or indirectly inducing CD4⁺ and CD8⁺ T-cell responses in the draining lymph nodes. The magnitude, breadth, and longevity of these responses are influenced by vaccine dose, spatiotemporal vaccine release kinetics, and immunoregulatory signals delivered with the antigen or released by other skin cells.

Fig. 4

Microarray patches (MAPs) enable precise, consistent, and minimally invasive administration of vaccine formulations (antigen ± adjuvant) to immunologically rich cutaneous microenvironments, whereas conventional intramuscular (IM) immunization bypasses the skin immune system, results in systemic exposure to vaccine ingredients, and causes pain.

Fig. 5

Representative images of different MAP concepts presented in the literature. a. Solid MAPs manufactured from polylactic acid (PLA). Adapted with permission from [220]. Copyright 2010, Elsevier. b. Coated MAPs fabricated from PLA. Adapted with permission from [221] under terms of the CC-BY 4.0 license (https://creativecommons.org/licenses/by/4.0/). Copyright 2020, the Authors. c. Polymer hollow MAPs. Adapted with permission from [222] under terms of the CC-BY 4.0 license. Copyright 2019, the Authors. d. Dissolvable MAPs produced from a mixture of carboxymethylcellulose and trehalose. Adapted with permission from [223]. Copyright 2011, Wiley-VCH. e. Hydrogel-forming MAPs created from a blend of poly(methylvinylether-co-maleic acid), poly(ethylene glycol), and sodium carbonate. Adapted with permission from [224]. Copyright 2018, American Chemical Society. f. Porous MAPs fabricated from PLA. Adapted with permission from [225]. Copyright 2007, Springer Nature. g. Hybrid MAPs with stainless steel stems and dissolving poly(vinyl alcohol)/sucrose tips. Adapted with permission from [226]. Copyright 2011, Elsevier. h. Hybrid MAPs with SU-8 microtube stems and dissolving maltose tips after 3 min skin application. Adapted with permission from [227]. Copyright 2013, American Institute of Physics. Unless otherwise indicated, scale bars = 500 μm.