Cancer Immunotherapy and Immunobiology Center, Hadassah-Hebrew University Medical Center, 9112001, Jerusalem, Israel.
Immunovative Therapies, Ltd, Malcha Technology Park, B1/F1, 9695101, Jerusalem, Israel.
J Transl Med. 2020 May 12;18(1):196. doi: 10.1186/s12967-020-02363-3.
We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X'. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an "anti-viral state", by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter.
Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.
我们提出了一种新型同种异体启动方法的基本原理,旨在为老年人提供一种通用的抗病毒疫苗,同时重塑衰老的免疫系统,以逆转免疫衰老和炎症衰老。这种方法有可能保护最脆弱的人群免受疾病的侵害,并为社会带来无法估量的经济效益。我们建议对健康的老年人进行同种异体启动,以提供对任何类型病毒感染进展的普遍保护,包括预防当前 COVID-19 感染的进展,以及导致 SARS-CoV-2 病毒或下一个“X 疾病”的任何未来变体。同种异体启动是 COVID-19 大流行的一种替代方法,如果引发中和抗体保护的疫苗接种策略失败或未能保护弱势老年人群体,它提供了一个后备方案。同种异体启动是使用目前正在临床应用中作为实验性癌症疫苗的激活、有意错配、体外分化和扩增的活 Th1 样细胞(AlloStim)进行的。多次皮内注射 AlloStim 会在循环中产生优势同种特异性 Th1/CTL 记忆细胞滴度,取代衰老免疫系统中耗尽的记忆细胞的优势。当遇到病毒时,同种特异性记忆细胞的旁观者激活会立即释放 IFN-γ,导致“抗病毒状态”的发展,旁观者激活先天细胞效应细胞和激活交叉反应性同种特异性 CTL。通过这种方式,非特异性激活同种特异性 Th1/CTL 引发了一系列时空免疫事件,从而限制了早期病毒滴度。在 IFN-γ 的情况下,从裂解的病毒感染细胞中释放内源性热休克蛋白(HSP)和 DAMPs,为原位疫苗接种创造了条件,导致病毒特异性 Th1/CTL 免疫。这些病毒特异性 Th1/CTL 提供了杀菌免疫和记忆,以防止疾病复发,同时增加了循环中能够应对下一次病毒接触的 Th1/CTL 池。
同种异体启动有可能为病毒疾病提供普遍保护,是逆转免疫衰老和对抗慢性炎症(炎症衰老)的策略。同种异体启动可作为抗病毒疫苗的佐剂,也可作为未知生物威胁和生物经济恐怖主义的对策。