Balmert Stephen C, Ghozloujeh Zohreh Gholizadeh, Carey Cara Donahue, Williams Li'an H, Zhang Jiying, Shahi Preeti, Amer Maher, Sumpter Tina L, Erdos Geza, Korkmaz Emrullah, Falo Louis D
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
iScience. 2022 Oct 21;25(10):105045. doi: 10.1016/j.isci.2022.105045. Epub 2022 Aug 30.
Sustainable global immunization campaigns against COVID-19 and other emerging infectious diseases require effective, broadly deployable vaccines. Here, we report a dissolvable microarray patch (MAP) SARS-CoV-2 vaccine that targets the immunoresponsive skin microenvironment, enabling efficacious needle-free immunization. Multicomponent MAPs delivering both SARS-CoV-2 S1 subunit antigen and the TLR3 agonist Poly(I:C) induce robust antibody and cellular immune responses systemically and in the respiratory mucosa. MAP vaccine-induced antibodies bind S1 and the SARS-CoV-2 receptor-binding domain, efficiently neutralize the virus, and persist at high levels for more than a year. The MAP platform reduces systemic toxicity of the delivered adjuvant and maintains vaccine stability without refrigeration. When applied to human skin, MAP vaccines activate skin-derived migratory antigen-presenting cells, supporting the feasibility of human translation. Ultimately, this shelf-stable MAP vaccine improves immunogenicity and safety compared to traditional intramuscular vaccines and offers an attractive alternative for global immunization efforts against a range of infectious pathogens.
针对新冠病毒和其他新出现的传染病开展可持续的全球免疫运动需要有效且可广泛部署的疫苗。在此,我们报告一种可溶解的微阵列贴片(MAP)新冠病毒疫苗,该疫苗靶向免疫反应性皮肤微环境,能够实现有效的无针免疫。递送新冠病毒S1亚基抗原和Toll样受体3激动剂聚肌苷酸-聚胞苷酸(Poly(I:C))的多组分MAP在全身和呼吸道黏膜中诱导强烈的抗体和细胞免疫反应。MAP疫苗诱导的抗体结合S1和新冠病毒受体结合域,有效中和病毒,并在高水平持续存在一年以上。MAP平台降低了所递送佐剂的全身毒性,并在无需冷藏的情况下保持疫苗稳定性。当应用于人体皮肤时,MAP疫苗激活皮肤来源的迁移性抗原呈递细胞,支持人体转化的可行性。最终,这种易于保存的MAP疫苗与传统肌肉注射疫苗相比提高了免疫原性和安全性,并为针对一系列传染性病原体的全球免疫努力提供了有吸引力的替代方案。