Development of Vectored ImmunoProphylaxis as a strategy against HIV

开发载体免疫预防作为抗 HIV 策略

• 批准号: 8411105
• 负责人: Alejandro Benjamin Balazs
• 金额: $ 15.66万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411105
• 关键词: AIDS prevention; Animals; Antibodies; Baltimore; CCR5 gene; CXCR4 gene; California; Clinical; Communicable Diseases; Dependovirus; Development; Doctor of Philosophy; Dose; Effectiveness; Elements; Engineering; Epitopes; Evolution; Exhibits; Failure; Funding; Future; Gene Transfer; Goals; Grant; Growth; HIV; HIV Infections; Hepatitis C; Human; Immune response; Immune system; Immunity; In Vitro; Infection; Infection prevention; Influenza; Institutes; Intravenous; Laboratories; Modeling; Molecular; Monoclonal Antibodies; Mucous Membrane; Mus; Muscle; Mutation; Positioning Attribute; Prevention; Process; Prophylactic treatment; Research; Research Personnel; Resistance; Role; Route; Surface; System; Technology; Testing; Titrations; Transgenes; Vaccination; Vaccines; Vagina; Viral; Virus; Work; cost; immunoprophylaxis; improved; in vivo; intraperitoneal; mouse model; neutralizing antibody; next generation; novel; pathogen; post-doctoral training; prevent; professor; promoter; public health relevance; research study; response; transmission process; vector

DESCRIPTION (provided by applicant): This proposal describes the framework of a transitional grant for Alejandro B. Balazs, PhD. The grant would be activated after Dr. Balazs obtains an assistant professor position and would provide funding for the initial years of work. Dr. Balazs is currently a postdoctoral scholar in David Baltimore's laboratory at the California Institute of Technology. Dr. Balazs' research is focused on engineering the immune system via gene transfer as a novel means of creating protection against infectious disease in a process termed Vectored ImmunoProphylaxis (VIP). This proposal is focused on extending the recent demonstration of protection against HIV infection in humanized mice by monoclonal antibodies delivered by VIP. The proposal aims to extend these findings by determining the in vivo potency of several recently described broadly neutralizing antibodies that, in vitro, exhibited greater potency and breadth of neutralization than those described previously. It will study the potential for VIP to prevent infection by transmitted founder strains of HIV. It also aims to model human-to-human transmissions and determine the degree of protection against HIV infection conferred by VIP in a second humanized mouse model that exhibits greater immunological function. Finally, it will examine the contribution of escape mutations to the failure of VIP when expressing low concentrations of neutralizing antibodies. Together, this work will expand our understanding of the potential of using neutralizing antibodies delivered by gene transfer as prophylaxis against HIV, and it will explore viral escape, which might undermine the effectiveness of this and other vaccine approaches in humans.

描述（由申请人提供）：本提案描述了Alejandro B的过渡性赠款框架。Balazs博士该赠款将在Balazs博士获得助理教授职位后启动，并为最初几年的工作提供资金。巴拉兹博士目前是加州理工学院大卫·巴尔的摩实验室的博士后学者。Balazs博士的研究重点是通过基因转移工程免疫系统，作为一种新的手段，在称为Vectored ImmunoProphylaxis（VIP）的过程中创造对传染病的保护。该建议的重点是延长最近的证明，保护免受HIV感染的人源化小鼠的单克隆抗体提供VIP。该提案旨在通过确定几种最近描述的广泛中和抗体的体内效力来扩展这些发现，这些抗体在体外表现出比先前描述的更大的中和效力和宽度。它将研究VIP预防艾滋病毒传播创始株感染的潜力。它还旨在模拟人与人之间的传播，并确定VIP在第二个人源化小鼠模型中对HIV感染的保护程度，该模型表现出更强的免疫功能。最后，它将检查逃逸突变对表达低浓度中和抗体时VIP失败的贡献。总之，这项工作将扩大我们对使用基因转移提供的中和抗体预防艾滋病毒的潜力的理解，并将探索病毒逃逸，这可能会破坏这种和其他疫苗方法在人类中的有效性。