IMMUNOGENICITY OF MEASLES VIRUS VACCINE STRAINS

麻疹病毒疫苗株的免疫原性

• 批准号: 5200732
• 负责人: J A BEELER
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200732
• 关键词: Indonesia; active immunization; age difference; antiviral antibody; cellular immunity; child (0-11); clinical trials; dietary supplements; drug administration rate /duration; genetic strain; human subject; human therapy evaluation; humoral immunity; immunity; infant human (0-1 year); interferon gamma; measles vaccine; measles virus; microorganism hemagglutinin; microorganism immunology; neutralizing antibody; nutrition related tag; passive immunization; retinoids; virus replication

Measles outbreaks continue to occur in unimmunized children and in older vaccines due to primary vaccine failure or waning immunity. Achieving protective immunity across all age groups requires several strategies including a better understanding of the optimal age for immunizing young infants, the optimal age for reimmunization, and knowledge about the factors that might enhance or diminish the response to currently available vaccines. Towards this end, this laboratory collaborates with several clinical investigators to evaluate the immune response to measles vaccine. In collaboration with Dr. Henry Pabst, we have completed studies that define the kinetics of the humoral and cell mediated immune response to the first dose of measles containing vaccine in 12 month old children. 80 children were immunized with vaccine containing the Moraten strain of measles virus and followed serially for 38 days. Neutralizing antibody and CMI response to measles HA plateaued by 28 days after immunization. Lymphoproliferative responses to tetanus and candida were depressed at 14 days after immunization but returned to baseline by day 38. The response to recall antigens were depressed 10-20%; in contrast, responses were depressed 80-90% following wild type infection. The predominant cytokine expressed by PBMCs after immunization was IFN-gamma with no change in IL4 or IL10 secretion suggesting that primary measles immunization primes for a predominantly TH1 type response. The impact of vitamin A supplementation on primary measles immunization (Schwarz strain) was studied in a placebo controlled double-blind trial in 9 month old infants in Indonesia in collaboration with Dr. Richard Semba. There was no significant difference between the vitamin treated and control groups in seroconversion rates or percent achieving protective neutralizing antibody titers. However, GMTs for infants in the placebo group who had maternal antibody at the time of immunization were higher than the GMTs for antibody positive infants in the vitamin a treated group suggesting synergy between passively acquired antibody and vitamin A in limiting vaccine virus replication. Studies to evaluate the optimal age for the second dose of measles vaccine are currently underway. Preliminary analysis of sera from over 237 children indicates that the second dose of measles vaccine is successful in seroconverting all children with primary vaccine failure and increases the percent with titers >120 from 94 to 99%. This level of immunity is necessary to achieve measles eradication in the US.

麻疹疫情继续发生在未接种疫苗的儿童和老年人中， 疫苗接种失败或免疫力下降。 实现 所有年龄组的保护性免疫需要几种策略 包括更好地了解年轻人接种疫苗的最佳年龄， 婴儿，再免疫的最佳年龄， 可能增强或减弱对当前 可用的疫苗。 为此，该实验室与 几名临床研究人员评估对麻疹的免疫反应 疫苗 与亨利帕布斯特博士合作，我们完成了 确定体液和细胞介导的免疫反应动力学的研究 12月龄婴儿对第一剂麻疹疫苗的反应 孩子 80名儿童接种了含有Moraten的疫苗 麻疹病毒株，并连续随访38天。 中和 麻疹HA的抗体和CMI反应在接种后28天达到平台 次免疫 对破伤风和念珠菌的抗增殖反应是 免疫后14天降低，但每天恢复到基线水平 38. 对回忆抗原的反应被抑制了10-20%;相反， 在野生型感染后，应答降低80-90%。 的 免疫后PBMC表达的主要细胞因子是IFN-γ 而IL 4或IL 10分泌无变化，提示原发性麻疹 免疫引发主要为TH 1型反应。 的影响 补充维生素A对初级麻疹免疫的影响（施瓦茨 菌株）在9个月的安慰剂对照双盲试验中进行了研究 与Richard Semba博士合作，在印度尼西亚的老年婴儿中进行研究。 那里 维生素处理组和对照组之间无显著差异 血清转化率或达到保护性的百分比 中和抗体滴度。 然而，安慰剂组婴儿的GMT 免疫时有母源抗体者， 比维生素a治疗的抗体阳性婴儿的GMT 提示被动获得抗体和维生素之间协同作用的组 限制疫苗病毒复制。 学评价研究 第二剂麻疹疫苗的最佳年龄目前 正在进行中 237例小儿血清学初步分析 表明第二剂麻疹疫苗成功地 所有初次疫苗接种失败的儿童发生血清转化， 滴度>120的百分比从94%到99%。 这种免疫力是 在美国实现麻疹根除是必要的。