Schnepp Bruce C, Johnson Philip R
Infectious Disease, The Children's Hospital of Philadelphia, Abramson Research Center, Room 1216J, 3615 Civic Center Blvd., Philadelphia, PA, 19104, USA,
Adv Exp Med Biol. 2015;848:149-67. doi: 10.1007/978-1-4939-2432-5_8.
This chapter discusses the emerging field of vector-mediated antibody gene transfer as an alternative vaccine for infectious disease, with a specific focus on HIV. However, this methodology need not be confined to HIV-1; the general strategy of vector-mediated antibody gene transfer can be applied to other difficult vaccine targets like hepatitis C virus, malaria, respiratory syncytial virus, and tuberculosis. This approach is an improvement over classical passive immunization strategies that administer antibody proteins to the host to provide protection from infection. With vector-mediated gene transfer, the antibody gene is delivered to the host, via a recombinant adeno-associated virus (rAAV) vector; this in turn results in long-term endogenous antibody expression from the injected muscle that confers protective immunity. Vector-mediated antibody gene transfer can rapidly move existing, potent broadly cross-neutralizing HIV-1-specific antibodies 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 limited promise.
本章讨论了载体介导的抗体基因转移这一新兴领域,它作为传染病的一种替代疫苗,特别聚焦于艾滋病病毒。然而,这种方法并不局限于HIV-1;载体介导的抗体基因转移的一般策略可应用于其他难以攻克的疫苗靶点,如丙型肝炎病毒、疟疾、呼吸道合胞病毒和结核病。这种方法是对经典被动免疫策略的改进,经典策略是向宿主施用抗体蛋白以提供抗感染保护。通过载体介导的基因转移,抗体基因通过重组腺相关病毒(rAAV)载体递送至宿主;这进而导致从注射的肌肉中产生长期内源性抗体表达,从而赋予保护性免疫。载体介导的抗体基因转移可迅速将现有的、强效的广泛交叉中和HIV-1特异性抗体引入临床。基因转移产物显示出与原始产物相同的效力和广度。该策略无需进行免疫原设计以及与适应性免疫系统相互作用来产生保护,而迄今为止,这种策略显示出的前景有限。