Immunoglobulins Delivered by AAV Vector for the Prevention of SIV Infection

AAV载体最近被用于运送单链抗体免疫粘附素(ScFVI)版本的恒河猴 具有中和SIV活性的猴抗体。在6个人中实现了持续高水平的scFVI 在9只恒河猴中，这6只猴对SIV攻击表现出一种杀菌屏障。九个中的三个 猴子产生了对它们收到的scFVI的抗体反应，这三只猴子没有受到保护 对抗SIV挑战。 将对两种不同的方法进行比较，以实现AAV载体传递这些病毒的真实免疫球蛋白验证 SCFVI。我们将确定交付真实的免疫球蛋白是否会降低抗-抗的频率 观察到了响应。我们将确定AAV载体是否可以用于运送二聚体分泌物 IGA和分泌型Ig A是否通过粘膜途径提供了更有效的SIV感染屏障。 最后，我们将确定抗体依赖的细胞毒性是否对保护性 4L6和5L7免疫球蛋白版本的效果。在恒河猴身上进行的这些实验的结果将告诉我们 并指导开发用于预防人类感染HIV-1的类似载体。

AAV vector has recently been used to deliver single chain Fv immunoadhesin (scFVI) versions of rhesus monkey antibodies with neutralizing activity against SIV. High, persisting levels of scFVI were achieved in 6 of 9 rhesus monkeys and these six exhibited a sterilizing barrier against SIV challenge. Three of the nine monkeys developed antibody responses to the scFVI that they received and these three were not protected against SIV challenge. Two different approaches will be compared for AAV vector delivery of the authentic IgG verison of these scFVIs. We will determine whether delivery of authentic IgG decreases the frequency with which anti-anti responses are observed. We will determine whether AAV vector can be used to deliver dimeric secretory IgA and whether secretory IgA provides a more effective barrier to SIV infection by the mucosal route. Finally, we will determine whether antibody-dependent cellular cytotoxicity is important for the protective effects of the IgG versions of 4L6 and 5L7. Results from these experiments in rhesus monkeys will inform and guide development of analogous vectors for the prevention of HIV-1 infection in humans.