MATERNO-FETAL HIV TRANSMISSION - MODEL FOR VACCINES

这项计划拨款是基于我们的初步研究限制高 与HIV-1 MN株gp 120反应的亲和抗体 中和结构域（gp 120 MN PND）降低母胎HIV 传输 此应用程序包括两个相互关联的艾滋病毒 由两个核心设施支持的输电项目。 第一 该项目将评估gp 120 MN PND的高亲和力抗体， HIV-1 MN株感染的母胎对。 表型和 这些抗体的功能将在HIV感染的孕妇中进行评估。 妇女及其新生儿。 胎儿结局（如HIV感染状况）将 与高亲和力MN-PND抗体的水平相关， 体外生物学功能（例如HIV-1-MN的中和）， 母体病毒载量。 根据先前获得的初步数据， 显示出母胎艾滋病毒缺乏 传播和这些MN-PND抗体的存在，我们建议在 第二个项目是开发艾滋病毒母婴传播阻断剂 疫苗 为此目的，MN-PND肽将与破伤风毒素缀合。 类毒素或PPD用于HIV血清阳性妇女的免疫接种， 一年内怀孕的可能性很高。 两 支持性核心设施包括：（a）疫苗生产设施 和动物试验设施，和（B）病毒生产、纯化 和中和核心，其中将获得HIV或其组分， 并将进行测定以测量生物学特性。 纯化MN-PND的功能（例如HIV-1-MN中和，ADCC） 抗体，并评估MN-PND疫苗的结果。 如果 如果成功，这种阻断传播的疫苗试验将在以后进行。 扩展至血清阴性健康个体，单独或联合 其他疫苗如HIV-1 gag疫苗。

This program grant is based on our preliminary studies limiting high affinity antibodies reactive with the HIV-1 MN strains gp120 Primary Neutralizing Domain (gp120 MN PND) to reduced materno-fetal HIV transmission. This application includes two interrelated HIV transmission projects supported by two core facilities. The first project will assess high affinity antibodies to the gp120 MN PND in materno-fetal pairs infected by the HIV-1 MN strain. The phenotype and function of these antibodies will be evaluated in HIV infected pregnant women and their neonates. Fetal outcme (e.g. HIV infection status) will be correlated with levels of high affinity MN-PND antibodies, with their in vitro biological function (e.g. neutralization of HIV-1-MN) and with maternal virus load. Based on preliminary data previously obtained here showing a significant correlation between the lack of materno-fetal HIV transmission and the presence of these MN-PND antibodies, we propose in the second project to develop a materno-fetal HIV transmission blocking vaccine. For that purpose MN-PND peptides will be conjugated to tetanus toxoid or to PPD for immunization of HIV seropositive women who have a high robability of becoming pregnant within one year. The two supporting core facilities consist of (a) an vaccine production facility and an animal testing facility, and (b) a virus production, purification and neutralization core, in which HIV or its components will be obtained from patients and assays will be conducted to measure the biological function (e.g. HIV-1-MN neutralization, ADCC) of purified MN-PND antibodies and to assess the outcome of the MN-PND vaccine. If successful, this transmission blocking vaccine trial will later be expanded to sero-negative healthy individuals, alone or in conjunction with other vaccines such as the HIV-1 gag vaccine.