Amano Tomokazu, Yu Hong, Amano Misa, Leyder Erica, Badiola Maria, Ray Priyanka, Kim Jiyoung, Ko Akihiro C, Achour Achouak, Weng Nan-Ping, Kochba Efrat, Levin Yotam, Ko Minoru S H
Elixirgen Therapeutics, Inc., Baltimore, MD, USA.
Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD, USA.
iScience. 2023 Mar 5;26(4):106335. doi: 10.1016/j.isci.2023.106335. eCollection 2023 Apr 21.
Intradermal delivery of self-replicating RNA (srRNA) is a promising vaccine platform. We have developed an srRNA that functions optimally at around 33°C (skin temperature) and is inactivated at or above 37°C (core body temperature) as a safety switch. This temperature-controllable srRNA (c-srRNA), when tested as an intradermal vaccine against SARS-CoV-2, functions when injected naked without lipid nanoparticles. Unlike most currently available vaccines, c-srRNA vaccines predominantly elicit cellular immunity with little or no antibody production. Interestingly, c-srRNA-vaccinated mice produced antigen-specific antibodies upon subsequent stimulation with antigen protein. Antigen-specific antibodies were also produced when B cell stimulation using antigen protein was followed by c-srRNA booster vaccination. We have thus designed a pan-coronavirus booster vaccine that incorporates both spike-receptor-binding domains as viral surface proteins and evolutionarily conserved nucleoproteins as viral internal proteins, from both severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. c-srRNA may provide a route to activate cellular immunity against a wide variety of pathogens.
自我复制RNA（srRNA）的皮内递送是一种很有前景的疫苗平台。我们开发了一种srRNA，它在约33°C（皮肤温度）时功能最佳，并在37°C或以上（核心体温）时失活作为安全开关。这种温度可控的srRNA（c-srRNA），在作为针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的皮内疫苗进行测试时，裸注射（不使用脂质纳米颗粒）即可发挥作用。与目前大多数可用疫苗不同，c-srRNA疫苗主要引发细胞免疫，几乎不产生或不产生抗体。有趣的是，接种c-srRNA的小鼠在随后用抗原蛋白刺激时产生了抗原特异性抗体。当先用抗原蛋白刺激B细胞，随后进行c-srRNA加强免疫时，也产生了抗原特异性抗体。因此，我们设计了一种泛冠状病毒加强疫苗，它包含严重急性呼吸综合征冠状病毒2和中东呼吸综合征冠状病毒的刺突受体结合域作为病毒表面蛋白，以及进化上保守的核蛋白作为病毒内部蛋白。c-srRNA可能为激活针对多种病原体的细胞免疫提供一条途径。
