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载体最近已用于递送具有针对SIV的中和活性的恒河猴抗体的单链Fv免疫粘附素（scFVI）形式。在9只恒河猴中的6只中实现了高的持续水平的scFVI，并且这6只表现出针对SIV攻击的灭菌屏障。九只猴子中的三只对它们接受的scFVI产生抗体应答，并且这三只没有受到SIV攻击的保护。 将比较两种不同的方法来递送这些scFVI的真实IgG版本。我们将确定真实IgG的递送是否降低观察到抗-抗应答的频率。我们将确定AAV载体是否可用于递送二聚体分泌型伊加，以及分泌型伊加是否通过粘膜途径对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4L 6和5L 7的IgG版本的保护作用是否重要。这些在恒河猴中的实验结果将为预防人类HIV-1感染的类似载体的开发提供信息和指导。