Immunoglobulins Delivered by AAV Vector for the Prevention of SIV Infection

AAV 载体传递的免疫球蛋白用于预防 SIV 感染

• 批准号: 8513256
• 负责人: Ronald C Desrosiers
• 金额: $ 66.79万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-18 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513256
• 关键词: Affect; Animals; Antibodies; Antibody Formation; Appearance; Biological Assay; Cell Culture Techniques; Cell Line; Complement; Dependovirus; Development; Exhibits; Frequencies; Future; Genetic Polymorphism; HIV-1; Human; IgG1; Immunity; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; In Vitro; Individual; Infection; J-Chain Immunoglobulins; Length; Macaca mulatta; Measurement; Mediating; Medicine; Monkeys; Mutation; Nature; Plasma; Population; Prevention; Publishing; Recombinant adeno-associated virus (rAAV); Route; SIV; Secretory Immunoglobulin A; System; Testing; Variant; adeno-associated viral vector; antibody-dependent cell cytotoxicity; base; improved; novel; protective effect; research study; response; vector

DESCRIPTION (provided by applicant): 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 version 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.

描述（由申请人提供）：AAV载体最近已被用于递送具有针对SIV的中和活性的单链Fv免疫粘附素（scFVI）版本的恒河猴抗体。 9 只恒河猴中有 6 只获得了高且持续的 scFVI 水平，这 6 只恒河猴表现出了针对 SIV 攻击的灭菌屏障。九只猴子中的三只对它们接受的 scFVI 产生了抗体反应，而这三只猴子没有受到 SIV 攻击的保护。 将比较两种不同的 AAV 载体递送这些 scFVI 的真实 IgG 版本的方法。我们将确定真实 IgG 的递送是否会降低观察到抗抗反应的频率。我们将确定 AAV 载体是否可用于递送二聚体分泌型 IgA，以及分泌型 IgA 是否可以为粘膜途径的 SIV 感染提供更有效的屏障。最后，我们将确定抗体依赖性细胞毒性对于 4L6 和 5L7 的 IgG 版本的保护作用是否重要。这些恒河猴实验的结果将为预防人类 HIV-1 感染的类似载体的开发提供信息和指导。