Intima Bioscience, Inc., New York, NY, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Cell Rep Med. 2022 Dec 20;3(12):100843. doi: 10.1016/j.xcrm.2022.100843. Epub 2022 Dec 7.
Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) genetically engineered to mimic natural physiological immunity induced upon viral infection of host cells. Cells engineered to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike as a representative viral antigen induce robust neutralizing antibodies in immunized non-human primates. Similar titers generated in this established non-human primate (NHP) model have translated into protective human neutralizing antibody levels in SARS-CoV-2-vaccinated individuals. Animals vaccinated with ancestral spike antigens and subsequently challenged with SARS-CoV-2 Delta variant in a heterologous challenge have an approximately 3 log decrease in viral subgenomic RNA in the lungs. This cellular vaccine is designed as a scalable cell line with a modular poly-antigenic payload, allowing for rapid, large-scale clinical manufacturing and use in an evolving viral variant environment.
尽管针对全球大流行，迅速将 COVID-19 疫苗进行临床转化，但仍有机会进行疫苗技术创新，以解决当前的局限性，并应对未来不可避免的大流行带来的挑战。我们描述了一种通用疫苗细胞（UVC），它经过基因工程设计，可模拟宿主细胞感染病毒时诱导的天然生理免疫。经过基因工程改造表达严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白作为代表性病毒抗原的细胞，可在免疫的非人类灵长类动物中诱导出强大的中和抗体。在这种已建立的非人类灵长类动物（NHP）模型中产生的类似滴度，已转化为 SARS-CoV-2 疫苗接种个体中保护性的人中和抗体水平。用祖先刺突抗原接种的动物，随后用 SARS-CoV-2 Delta 变体在异源挑战中进行挑战，其肺部的病毒亚基因组 RNA 减少了约 3 个对数级。这种细胞疫苗被设计为一种可扩展的细胞系，具有模块化的多抗原有效载荷，允许在不断演变的病毒变异环境中快速进行大规模临床制造和使用。
