Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy.
Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy.
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DOI：
10.3390/v14122727
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发表时间：
2022-12-06
期刊：
影响因子：
--
通讯作者：
Mittal SK
中科院分区：
文献类型：
--
作者：
Wang WC;Sayedahmed EE;Mittal SK
基于腺病毒的载体系统是疫苗开发和基因治疗应用的有前途的平台。AdV载体的施用增强了强大的先天免疫，导致针对载体和转基因抗原（如果适用的话）的体液和细胞免疫应答的发展。使用高剂量（1011-1013病毒颗粒）的AdV载体，特别是用于基因治疗应用，可能由于先天免疫应答水平过高、载体与血液因子相互作用或肝脏和脾脏中高水平的载体转导而导致载体毒性。此外，人类中AdV感染的高流行率或首次接种AdV载体导致产生载体特异性免疫应答，通常称为预先存在的载体免疫。在使用倾向于预先存在的载体免疫的AdV载体后，其显著降低了载体效率。已经开发了几种方法来克服这个问题。利用罕见的人腺病毒类型或非人腺病毒是逃避预先存在的载体免疫的主要策略。使用异源病毒载体、衣壳修饰和载体包封是逃避载体免疫的替代方法。载体可以优化的临床应用与全面的知识腺病毒载体免疫，毒性和规避策略。
An adenoviral (AdV)-based vector system is a promising platform for vaccine development and gene therapy applications. Administration of an AdV vector elicits robust innate immunity, leading to the development of humoral and cellular immune responses against the vector and the transgene antigen, if applicable. The use of high doses (1011–1013 virus particles) of an AdV vector, especially for gene therapy applications, could lead to vector toxicity due to excessive levels of innate immune responses, vector interactions with blood factors, or high levels of vector transduction in the liver and spleen. Additionally, the high prevalence of AdV infections in humans or the first inoculation with the AdV vector result in the development of vector-specific immune responses, popularly known as preexisting vector immunity. It significantly reduces the vector efficiency following the use of an AdV vector that is prone to preexisting vector immunity. Several approaches have been developed to overcome this problem. The utilization of rare human AdV types or nonhuman AdVs is the primary strategy to evade preexisting vector immunity. The use of heterologous viral vectors, capsid modification, and vector encapsulation are alternative methods to evade vector immunity. The vectors can be optimized for clinical applications with comprehensive knowledge of AdV vector immunity, toxicity, and circumvention strategies.
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