Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity.
Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity.
复制标题
DOI：
10.1016/j.isci.2023.106335
复制
发表时间：
2023-04-21
期刊：
影响因子：
5.8
通讯作者：
Ko MSH
中科院分区：
文献类型：
--
作者：
Amano T;Yu H;Amano M;Leyder E;Badiola M;Ray P;Kim J;Ko AC;Achour A;Weng NP;Kochba E;Levin Y;Ko MSH
自我复制RNA（srRNA）的皮内递送是一种有前途的疫苗平台。我们已经开发出一种srRNA，它在33°C左右（皮肤温度）时发挥最佳作用，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），当作为针对SARS-CoV-2的皮内疫苗进行测试时，在没有脂质纳米颗粒的情况下裸注射时发挥作用。与大多数目前可用的疫苗不同，c-srRNA疫苗主要引起细胞免疫，很少或没有抗体产生。有趣的是，c-srRNA接种的小鼠在随后用抗原蛋白刺激后产生抗原特异性抗体。当使用抗原蛋白刺激B细胞后进行c-srRNA加强接种时，也产生抗原特异性抗体。因此，我们设计了一种泛冠状病毒加强疫苗，该疫苗结合了作为病毒表面蛋白的刺突受体结合结构域和作为病毒内部蛋白的进化保守核蛋白，来自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。c-srRNA可以提供激活针对多种病原体的细胞免疫的途径。我们开发了一种用于皮肤递送的mRNA疫苗平台，无需纳米颗粒该疫苗主要引起细胞免疫，很少或不产生抗体该疫苗用作初免或加强剂时可增强抗体产生我们使用病毒RBD和核蛋白设计了泛冠状病毒加强疫苗免疫;分子生物学;病毒学
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. We developed an mRNA vaccine platform for skin delivery without nanoparticles The vaccine mainly elicits cellular immunity with little or no antibody production The vaccine enhances antibody production when used as a prime or a booster We designed a pan-coronavirus booster vaccine using viral RBDs and nucleoproteins Immunity; Molecular biology; Virology
登录
查看更多内容
影响因子：
6.7
作者：
Beitzel BF;Bakken RR;Smith JM;Schmaljohn CS
通讯作者：
Schmaljohn CS
DOI：
10.2471/blt.10.079426
发表时间：
2011-03-01
期刊：
Bulletin of the World Health Organization: International Journal of Public Health
影响因子：
--
作者：
Hickling, JK;Jones, KR;Kristensen, D
通讯作者：
Kristensen, D
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
DOI：
10.1002/cpz1.39
发表时间：
2021-02-01
期刊：
Current protocols
影响因子：
--
作者：
Henderson, Jordana M;Ujita, Andrew;Houston, Michael E
通讯作者：
Houston, Michael E
影响因子：
14.9
作者：
JOHANNING, FW;CONRY, RM;CURIEL, DT
通讯作者：
CURIEL, DT