MUCOSAL SECRETION KINETICS OF THE PG9 BROADLY NEUTRALIZING ANTIBODY AGAINST HIV

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目的：研究抗体PG9在全身和粘膜中的药代动力学。 大多数成功的抗病毒疫苗都会诱导中和抗体，这种抗体通常与保护作用密切相关。对于HIV，已经证明被动转移中和抗体可以在最好的可用的动物模型中提供对病毒挑战的保护。因此，人们普遍认为，激发中和抗体反应将是有效的艾滋病毒疫苗的关键组成部分。鉴于接种疫苗的人可能接触到的病毒的多样性，这种抗体应该具有广泛的中和作用。 抗体PG9显示出广度和效力的非凡组合，这表明疫苗诱导的这种类型的抗体很可能在通过接种疫苗所能达到的血清浓度下提供保护。因此，PG9很可能成为了解Env结构、构象和功能的有用试剂。这些研究特别阐明了gp120的V2和V3环的保守区作为免疫原设计的目标的潜力。 进度： 两只动物被被动地注入PG9抗体。被动输注后14天取样检测血液和粘膜抗体水平。所获得的结果证实了抗体进入粘膜腔内的运输。这项研究的数据将用于SIV病毒挑战研究中被动输注的最终方案设计。 这项研究使用了动物服务、CPI和免疫学服务。 出版物： 没有。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To assess the systemic and mucosal pharmacokinetics of antibody PG9. Most successful anti-viral vaccines induce neutralizing antibodies, which are typically a strong correlate of protection. For HIV, it has been shown that passive transfer of neutralizing antibodies can provide protection against viral challenge in the best available animal models. Therefore, it is widely argued that the elicitation of a neutralizing antibody response will be a crucial component of an effective vaccine against HIV. Such antibodies should be broadly neutralizing given the diversity of viruses to which a vaccinee may be exposed. The antibody PG9 displays a remarkable combination of breadth and potency that suggests that vaccine-induced antibodies of this type would likely provide protection at serum concentrations that would be achievable by vaccination. Thus, PG9 will likely be useful reagent for understanding Env structure, conformation, and function. These studies have, in particular, illuminated the potential of conserved regions of the V2 and V3 loop of gp120 to serve as a target for immunogen design. PROGRESS: Two animals were passively infused with the PG9 antibody. Blood and mucosal antibody levels were determined by sampling for 14 days following passive infusion. The obtained results confirmed the transport of the antibodies into the mucosal lumen. Data from this study will be used in the final protocol design for the passive infusion in SHIV viral challenge studies. This research used Animal Services, CPI and Immunology Services. PUBLICATIONS: None.