LONG TERM FOLLOW-UP AFTER HIGH TITER MEASLES VACCINE

我们建议对接受高效价麻疹疫苗的人进行评估 通过将它们与接受者进行比较来证明长期不良反应 低滴度疫苗对生存、营养状况和免疫学的影响 参数。这些儿童接种了高、中和标准滴度。 麻疹(分别约为105.4、104.5和103.5 pfu/剂) 1987-1989年的疫苗。1991年的一项跟踪研究显示， 女性高滴度疫苗接种者的死亡率。我们建议 确定高滴度疫苗接种者死亡率是否增加 在接种疫苗后持续了3年以上，如果有差异 在营养状况和免疫学参数中可以在 幸存者按性别和接种疫苗剂量分列。我们预计会确认 大约1500-1700名原始学习儿童，包括600-700名 接种高滴度疫苗的儿童。孩子们将受到监控 三年半期间的死亡率和疾病发展情况。 对7种抗原的迟发性超敏反应皮肤测试将是 对600名儿童(300名高滴度受试者)进行了检查。其他内容 免疫学研究将在整组随机样本上进行(通过 第一年300名儿童的性别和疫苗剂量)，总计 白细胞计数和分类，外周血单核细胞 检测外周血中CD4、CD8、CD3、NK、CD45RA和 CD45RO阳性细胞。淋巴细胞增殖率将被测定 接触有丝分裂原(PHA和抗CD3)和抗原前后 (麻疹和破伤风)和T细胞细胞因子的产生(IL-2、IL-4、干扰素- 伽马)将被测量。更多的细胞将被冷冻在RNA-zol中- 70度用于后续的mRNA和细胞因子mRNA分析，细胞将 提供给Peter Dowling博士用于PCR-RT检测持久性 感染。将对血浆进行麻疹抗体和等量的麻疹检测 细胞和血浆将被保存下来，以供未来研究。最多300个 更多的孩子将在第二年和以后学习。 从第一年的研究结果中可以看出，这一数字是几年前的。这些 数据将使我们能够检测持续的免疫差异，并 更好地了解延迟起病的发病机制 高滴度疫苗接种后死亡率增加。这项研究将 提供对开发和开发非常重要的信息 对新的麻疹疫苗的评价。

We propose to evaluate recipients of high titer measles vaccines for evidence of long-term adverse effects by comparing them with recipients of lower titer vaccines for survival, nutritional status, and immunologic parameters. These children received high, medium, and standard titer (approximately 105.4, 104.5, and 103.5 pfu/dose, respectively) measles vaccines in 1987-1989. A followup study in 1991 revealed increased mortality among female high titer vaccine recipients. We propose to determine if the increased mortality among high titer vaccines recipients has persisted for more than 3 years after vaccination and if differences in nutritional status and immunologic parameters can be detected among survivors by sex and dose of vaccine received. We anticipate identifying approximately 1500-1700 of the original study children, including 600-700 children who receive high titer vaccines. The children will be monitored for mortality and the development of illnesses over a 3 1/2 year period. Skin tests for delayed type hypersensitivity to 7 antigens will be performed on 600 children (300 high titer recipients). Additional immunologic studies will be performed on a block randomized sample (by sex and vaccine dose) of 300 children in the first year including total white blood count and differential, peripheral blood mononuclear cell phenotyping to determine the percent CD4, CD8, CD3, NK, CD45RA, and CD45RO positive cells. Lymphocyte proliferation will be determined before and after exposure to mitogens (PHA and anti-CD3) and antigens (measles and tetanus), and T cell cytokine production (IL-2, IL-4, IFN- gamma) will be measured. Additional cells will be frozen in RNA-zol at - 70 degrees for subsequent mRNA and cytokine mRNA analysis and cells will be provided to Dr. Peter Dowling for PCR-Rt to detect persistent infections. Plasma will be tested for measles antibody and aliquots of cells and plasma will be preserved for future studies. Up to 300 additional children will be studied in the second year and in subsequent years, as indicated from the results of the first year studies. These data will allow us to detect persistent immunologic differences and to obtain better understanding of the pathogenesis for delayed onset increased mortality following high titer vaccines. This study will provide information that will be important for the development and evaluation of new measles vaccines.