MEASLES VACCINES--IMMUNE RESPONSES AND ATYPICAL MEASLES

麻疹疫苗——免疫反应和非典型麻疹

• 批准号: 2397300
• 负责人: Diane E Griffin
• 金额: $ 34.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2397300
• 关键词: Macaca mulatta; active immunization; antibody formation; antiviral antibody; attenuated microorganism; cytokine; human tissue; immunity; laboratory mouse; live vaccine; measles; measles vaccine; measles virus; tissue /cell culture; vaccine development; vector vaccine

DESCRIPTION: Recovery from measles is associated with life-long immunity that is reflected by the persistence of antibody. Protection after infection with wt virus or after live vaccine is closely associated with levels of neutralizing and hemagglutination-inhibiting antibody; experiences in immunosuppressed children also suggests that a virus-specific cellular immune response is essential for recovery. The currently licensed live attenuated measles virus vaccine is safe and effective when given at 9-15 months of age, but the vaccine is less effective in infants under the age of 9 months, and urban outbreaks have recently involved many young infants. Although immunization of infants as young as 4-6 months has been successful using a 10-100 fold higher dose of vaccine virus, such immunization has been associated with a poorly understood increase in susceptibility to subsequent infections and has been abandoned as a strategy for improving the vaccine and lowering the age of immunization. An inactivated vaccine was one of the earliest measles vaccines introduced. After 3 doses of alum-precipitated, formalin-inactivated vaccine, neutralizing antibody adequate to protect against wild-type viruses was present for a few months, but protection rapidly waned. In addition, approximately 15% of children immunized with this vaccine who subsequently contracted measles developed a severe form of the disease known as atypical measles. This complication has been ascribed to the low levels of antibody to the fusion protein that were induced by the inactivated vaccine, but this pathogenic mechanism has never been proven. Failure to understand the pathogenesis of atypical measles continues to impede the development of newer vaccines for all paramyxoviruses. The current proposal represents a competitive renewal of an original award granted in 1993 to investigate immune responses to measles and atypical measles in non-human primates. In this proposal the investigators propose follow-up studies and other work to determine the pathogenesis of atypical measles, characterize the immune responses to prototype live and inactivated vaccines, and to continue development of cDNA-based measles vaccines. The specific aims of the proposal are: 1) to characterize the immune responses to formalin-inactivated vaccine and live attenuated vaccines by comparing the specificities and biological properties of anti-measles virus antibodies, T cell effector functions, and the cytokines induced by immunization; 2) to define the nature of the immune responses after challenge with wild-type measles virus in unimmunized monkeys and in monkeys previously immunized with live or formalin-inactivated vaccines; and 3) to determine the nature of the immune response to and the efficacy of H, F an d/or N cDNA vaccines delivered by different routes of inoculation in monkeys.

描述：从麻疹中恢复与终身免疫有关 抗体的持久性反映了这。 保护之后 WT病毒或现场疫苗后感染与 抑制抗体的中和水平；经验 在免疫抑制儿童中还表明病毒特异性细胞 免疫反应对于恢复至关重要。 目前有执照的活体麻疹病毒疫苗是安全的， 在9-15个月大时给予生效，但疫苗较少 在9个月以下的婴儿中有效，城市爆发有 最近涉及许多年轻婴儿。 尽管婴儿免疫 年轻的4-6个月已经成功使用了10-100倍的剂量 疫苗病毒，这种免疫与不良 了解后来感染的易感性增加，并且已经 被放弃作为改善疫苗并降低年龄的策略 免疫。 灭活的疫苗是引入最早的麻疹疫苗之一。 经过3剂明矾定位的福尔马林灭活疫苗后， 中和足以预防野生型病毒的抗体是 出席了几个月，但保护迅速下降。 此外， 大约15％的儿童用这种疫苗免疫的儿童 收缩的麻疹形成了一种严重的疾病形式，称为非典型疾病 麻疹。 这种并发症已归因于低水平的抗体 致灭活疫苗诱导的融合蛋白，但这 致病机制从未得到证明。 不了解 非典型麻疹的发病机理继续阻碍 所有参氧病毒的较新疫苗。 当前的提案代表了原始奖项的竞争续约 1993年授予研究对麻疹和非典型的免疫反应 非人类灵长类动物的麻疹。 在此提案中，调查人员提出了 后续研究和其他工作以确定非典型的发病机理 麻疹，表征对原型的免疫反应生存和灭活 疫苗，并继续开发基于cDNA的麻疹疫苗。 这 该提案的具体目的是：1）表征免疫反应 通过比较 抗膜病毒的特异性和生物学特性 抗体，T细胞效应函数和由 免疫； 2）定义免疫反应的性质 在未免疫猴子和猴子中挑战野生型麻疹病毒 以前用现场或福尔马林灭活的疫苗免疫；和3）到 确定免疫反应的性质和h，f A的功效 通过接种不同的接种途径在 猴子。