B Cell Core

摘要：B细胞核心-核心2 母婴传播(MTCT)仍然是一个全球健康问题，并导致许多婴儿/儿童感染艾滋病毒-1 每年都有感染。一种可减少因母乳喂养而传播HIV-1的疫苗的开发 将在资源匮乏的环境中利用母乳喂养的既定好处，同时减少感染 费率。该HIVRAD应用程序的目的是确定一种疫苗策略是否适用于婴儿、母亲或两者， 可因母乳喂养而减少母婴传播。本申请中提出的研究将使用恒河猴。 模型来确定疫苗减少母乳喂养相关母婴传播的能力。这个B细胞核心将 量化那些可能与感染风险相关的反应，以确定那些对 并为今后的人体研究提供初步数据。具体地说，在目标1中，我们将量化 母婴疫苗激发的抗体的功能活性、亲和力和识别表位 养生法。在目标2中，我们将创建一种重组env蛋白抗原特异性试剂来量化频率 以及母婴中疫苗诱导的环境特异性B细胞反应的表型。这项工作将考验 假设疫苗诱导的抗原特异性B细胞频率较高与更强大的 ADCC，更高的抗体亲和力，血浆抗体与更多表位的结合，以及以下更好的保护 挑战。最后，在目标3中，我们将定义环境疫苗接种婴儿的B细胞库 产妇接种疫苗。使用为AIM 2制造的相同的重组Env蛋白抗原特异性试剂，我们 将从婴儿中分离婴儿抗原特异性B细胞进行基因分析和单抗(MAb) 生产以检验胎盘转移的母体抗体将识别相同的假说 与婴儿的表位相同；因此，来自婴儿的单抗将具有相同的活性、亲和力和表位模式 与来自母亲的血浆抗体相比，具有特异性。B细胞核心将向 计划并极大地提高我们对B细胞反应的理解 HIV-1的母婴传播。

ABSTRACT: B Cell Core—Core 2 Mother-to-child transmission (MTCT) remains a global health problem and results in many infant/child HIV-1 infections each year. Development of a vaccine that can reduce HIV-1 transmission due to breastfeeding would leverage the established benefits of breastfeeding in resource poor settings while decreasing infection rates. The purpose of this HIVRAD application is to determine if a vaccine strategy in infants, mothers, or both, could reduce MTCT due to breastfeeding. The studies proposed in this application will use a rhesus macaque model to determine the ability of a vaccine to reduce breastfeeding associated MTCT. This B Cell Core will quantify those responses that may correlate with infection risk to determine those responses critical for protection and to provide preliminary data for future human studies. Specifically, in Aim 1, we will quantify the functional activity, avidity, and recognized epitopes of antibodies elicited by maternal and infant vaccine regimens. In Aim 2, we will create a recombinant Env protein antigen-specific reagent to quantify the frequency and phenotype of vaccine-elicited Env-specific B cell responses in mothers and infants. This work will test the hypothesis that a higher frequency of vaccine-elicited antigen-specific B cells correlates with more potent ADCC, higher antibody avidity, binding of plasma antibodies to more epitopes, and greater protection following challenge. Finally, in Aim 3, we will define the B cell repertoire of Env-vaccinated infants in the setting of maternal vaccination. Using the same recombinant Env protein antigen-specific reagent made for Aim 2, we will sort infant antigen-specific B cells from infants for gene analysis and monoclonal antibody (mAb) production to test the hypothesis that placentally transferred maternal antibodies will recognize the same epitopes as the infant; such that mAbs from infants will have the same patterns of activity, avidity, and epitope specificity when compared with plasma antibody from mothers. The B Cell Core will provide critical data to the Program and significantly advance our understanding of B Cell responses required for protection against MTCT of HIV-1.