Antibody Effector Function and Virology

在DNA素数、MVA Boost模型中要用到的这一应用项目中，唯一的免疫关联 到目前为止，对黏膜攻击的保护作用是GM-CSF介导的疫苗亲和力 一种与挑战病毒的包膜结合的抗体。保护机制尚不清楚，但 暗示了体液免疫反应的重要作用。病毒学和抗体检测的目标 因此，CORE将研究(一)基于GM-CSF的抗体保护机制(项目一)，(二) 促进肠道粘膜内体液免疫的新策略(项目二)，和(Iii)疫苗和 攻击诱导的抗体特异性(NHP单抗核心)。病毒学核心是 这些研究将评估中和和Fc介导的抗体激活是否与 疫苗诱导的保护。我们将专注于粘膜分泌物和血浆中的抗体来对抗病毒 Env和Gag蛋白。所述中和抗体成分通过与 病毒粒子相关形式的环境病毒和防止感染的目标细胞。虽然中和抗体很可能是 作为疫苗的关键组成部分，到目前为止还没有人诱导出能介导中和 基因多样化的病毒，这一特征对于保护感染HLV-1的人类至关重要。其他非中和 抗体激活与预防获得性免疫和疾病有关 进步。这些包括识别感染细胞表面表达的环境病毒，导致 细胞裂解(ADCC)除了增强可能有助于病毒其他非裂解机制之外 抑制(ADCVI)。最后，HIV-1和SIV通过生殖器粘膜的传播与 基因瓶颈，因此我们将确定在接种疫苗的人中建立感染的变异的特征 并控制猴子，以确定疫苗诱导的抗体是否对环境施加了选择性压力。 具体地说，病毒学核心将决定外周和粘膜中的免疫球蛋白和免疫球蛋白A是否介导 抗体活性与疫苗接种后对阴道内攻击的免疫保护有关 调查筛分效应是否明显。

In the DNA prime, MVA boost model to be used in Project One of this applicafion, the only immune correlate of protection against mucosal challenge identified thus far is the GM-CSF mediated avidity of vaccine-elicited anfibody binding to the envelope ofthe challenge virus. The mechanism for protecfion is unknown but suggests an important role for the humoral immune response. The goals of the Virology and Anfibody Assay Core are therefore to investigate (i) a mechanism for GM-CSF-based antibody protection (Project One), (ii) novel strategies for promofing humoral immunity within the gut mucosa (Project Two), and (iii) vaccine and challenge induced anfibody specificities (NHP Monoclonal Anfibody Core). The Virology Core is central to these studies and will assess whether neutralizing and Fc-mediated anfibody acfivifies correlate with vaccine-induced protecfion. We will focus on antibodies within mucosal secretions and plasma against viral proteins Env and Gag. The neutralizing antibody component mediates antiviral activity by binding to the virion associated form of Env and preventing infection of a target cell. While neutralizing anfibodies are likely to be a critical component of a vaccine, to date no one has elicited Nabs that can mediate neutralizafion of genetically diverse viruses, a feature that is critical for protection of HlV-1 infected humans. Other nonneutralizing antibody acfivifies have been associated with protection against acquisifion and disease progression. These involve recognition ofthe Env expressed on the surface of an infected cell, leading to lysis of that cell (ADCC) in addition to augmenting other non-lytic mechanisms that may contribute to viral suppression (ADCVI). Finally, transmission of HIV-1 and SIV across the genital mucosa is associated with a genefic bottleneck, and we will therefore characterize the variants that establish infection in the vaccinated and control monkeys to determine whether vaccine-induced antibodies imposed selective pressure on Env. Specifically, the Virology Core will determine whether peripheral and mucosal IgG and IgA-mediated antibody activities correlate with immune protection against intravaginal challenge following vaccination and investigate whether a sieve effect is evident.