LONG TERM FOLLOW-UP AFTER HIGH TITER MEASLES VACCINE

我们建议对高滴度麻疹疫苗接种者进行评估， 通过与接受者进行比较来证明长期不良反应 较低滴度疫苗的存活率，营养状况和免疫学 参数 这些儿童接受高、中、标准滴度 （分别约为105.4、104.5和103.5 pfu/剂）麻疹 1987-1989年的疫苗。 1991年的一项后续研究显示， 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的增加是否 疫苗接种后持续3年以上， 在营养状况和免疫参数中可以检测到 按性别和接种疫苗剂量分列的幸存者。 我们预计会发现 大约1500-1700名最初的研究儿童，包括600-700名 接种高滴度疫苗的儿童。 孩子们会被监控 在三年半的时间里，死亡率和疾病的发展。 将对7种抗原进行迟发型超敏反应皮肤试验， 在600名儿童中进行（300名高滴度受体）。 额外 免疫学研究将在区组随机化样品上进行（通过 性别和疫苗剂量），包括总数 白色血细胞计数和分类，外周血单核细胞 表型分析以确定CD 4、CD 8、CD 3、NK、CD 45 RA和 CD 45 RO阳性细胞。 将测定淋巴细胞增殖 暴露于有丝分裂原（PHA和抗CD 3）和抗原之前和之后 （麻疹和破伤风）和T细胞细胞因子产生（IL-2、IL-4、IFN-γ）。 gamma）将被测量。 将其他细胞冷冻在RNA-zol中， 70度进行随后的mRNA和细胞因子mRNA分析，细胞将 提供给Peter Dowling博士进行PCR-Rt，以检测持续性 感染. 将对血浆进行麻疹抗体检测， 细胞和血浆将被保存用于将来的研究。 高达300 在第二年和随后的一年中，将对更多的儿童进行研究。 从第一年的研究结果来看， 这些 数据将使我们能够检测持久的免疫差异， 更好地了解延迟发作的发病机制 接种高滴度疫苗后死亡率增加。 本研究将 提供对发展至关重要的信息， 评价新的麻疹疫苗。

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.