032 A multicomponent skin-targeted COVID-19 vaccine elicits robust humoral and cellular immune responses

Considerable progress has been made toward development of COVID-19 vaccines in the past year However, there is still a need for painless, self-administered, shelf-stable, and efficacious SARS-CoV-2 vaccines to enable sustainable immunization programs against COVID-19 To address this need, we hypothesized that harnessing the immune-responsive cutaneous microenvironment using microarray patches (MAPs) to deliver integrated SARS-CoV-2 vaccine components would bring together biologic advantages of targeting the endogenous immune circuitry of the skin with a thermostable and user-friendly cutaneous vaccine delivery platform We show that immunologically rich cutaneous microenvironments in both murine and human skin can be efficiently targeted using our 3D printing-enabled dissolving MAPs to deliver a recombinant SARS-CoV-2 protein antigen, with or without an innate immune agonist Immunization of mice with vaccine-loaded MAPs generates robust antibody and cellular immune responses, and multicomponent (antigen plus adjuvant) MAP vaccination improves the induced antigen-specific immune responses, such as virus-specific Th1 and IgG2c responses, which are vital for control of SARS-CoV-2 viral infection Notably, multicomponent MAP vaccination results in increased immune responses compared to immunization via traditional intramuscular injection, and MAP immunization obviates adverse effects of intramuscular delivery of adjuvants, suggesting improved safety and efficacy compared to conventional vaccination routes These results are supported by our translational studies utilizing freshly-excised human skin, suggesting that multicomponent MAPs induce greater expression of co-stimulatory molecules by human skin-migratory DCs, which may contribute to enhanced immune responses Ultimately, the simplicity, thermostability, immunogenicity, and versatility of MAPs may enable novel vaccination strategies and increase the effectiveness of global immunization campaigns against SARS-CoV-2 and other existing or novel pathogens