MATERNO-FETAL HIV TRANSMISSION - MODEL FOR VACCINES

这项计划的拨款是基于我们的初步研究限制高 与HIV-1 MN株gp120主要反应的亲和抗体 中和结构域(Gp120 MN PND)用于降低母婴HIV 变速箱。此应用程序包括两个相互关联的HIV 由两个核心设施支持的输电项目。第一 该项目将评估gp120 MN PND的高亲和力抗体 感染HIV-1 MN毒株的母婴配对。表型和 这些抗体的功能将在感染艾滋病毒的孕妇中进行评估 妇女和她们的新生儿。胎儿疾病(例如艾滋病毒感染状态)将 与高亲和力MN-PND抗体水平相关，与其 体外生物学功能(如中和HIV-1-MN)和 母体病毒载量。根据之前在这里获得的初步数据 表明母婴艾滋病病毒携带者之间存在显著的相关性 这些MN-PND抗体的传播和存在，我们在 第二个项目是开发母婴传播阻断系统 疫苗。为此，MN-PND多肽将与破伤风偶联 类毒素或PPD用于HIV血清阳性妇女的免疫接种 在一年内怀孕的可能性很高。两个人 辅助核心设施包括：(A)疫苗生产设施 和动物试验设施，以及(B)病毒生产、提纯 和中和核心，在其中将获得艾滋病毒或其成分 从患者和化验将进行测量生物 纯化的MN-PND的功能(如HIV-1-MN中和，ADCC) 并评估MN-PND疫苗的效果。如果 成功，这一传播阻断疫苗试验将于晚些时候 扩大到血清阴性的健康个体，单独或联合 与其他疫苗，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.