The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Curr Opin HIV AIDS. 2014 May;9(3):250-6. doi: 10.1097/COH.0000000000000056.
In the present review, we will discuss the emerging field of vector-mediated antibody gene transfer as an alternative HIV vaccine. This approach is an improvement over classical passive immunization strategies that administer antibodies to the host to provide protection from infection. With vector-mediated gene transfer, the antibody gene is delivered to the host, resulting in long-term endogenous antibody expression from the injected muscle that confers protective immunity.
Large numbers of very potent and broadly neutralizing HIV antibodies have recently been isolated and characterized. Vector-mediated antibody gene transfer allows one to immediately use these antibodies as a vaccine. Gene transfer studies in both mice and monkeys demonstrate long-term antibody expression in serum from a single injection at concentrations that provide sterilizing immunity.
Vector-mediated antibody gene transfer can rapidly move existing, potent anti-HIV molecules into the clinic. The gene transfer products demonstrate a potency and breadth identical to the original product. This strategy eliminates the need for immunogen design and interaction with the adaptive immune system to generate protection, a strategy that so far has shown little promise.
在本综述中,我们将讨论新兴的载体介导的抗体基因转移作为一种替代 HIV 疫苗的方法。与传统的被动免疫策略(向宿主施用抗体以提供免受感染的保护)相比,这种方法有所改进。通过载体介导的基因转移,将抗体基因递送到宿主,从而导致从注射肌肉中产生长期的内源性抗体表达,从而提供保护性免疫。
最近已经分离和鉴定了大量非常有效和广谱中和 HIV 的抗体。载体介导的抗体基因转移可以立即将这些抗体用作疫苗。在小鼠和猴子中的基因转移研究表明,单次注射即可在血清中产生长期的抗体表达,其浓度可提供杀菌性免疫。
载体介导的抗体基因转移可以迅速将现有的有效抗 HIV 分子推向临床。基因转移产物表现出与原始产物相同的效力和广度。这种策略消除了对免疫原设计和与适应性免疫系统相互作用以产生保护的需求,迄今为止,这种策略几乎没有显示出任何希望。