CYTOTOXIC T-LYMPHOCYTE RESPONSES TO MEASLES IN W AFRICA

西非地区麻疹的细胞毒性 T 淋巴细胞反应

• 批准号: 3149841
• 负责人: HILTON C WHITTLE
• 金额: $ 11.7万
• 依托单位: MEDICAL RESEARCH COUNCIL
• 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 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3149841
• 关键词: Africa; B lymphocyte; MHC class I antigen; active immunization; attenuated microorganism; cell mediated lymphocytolysis test; cellular immunity; child (0-11); cytotoxic T lymphocyte; epitope mapping; fusion gene; human subject; measles; measles vaccine; measles virus; nucleic acid sequence; transfection; vaccinia virus; virus antigen

The broad long term aim of this Project is to gain knowledge of immunity to measles effected by cytotoxic T lymphocytes (CTL) in West Africans infected with, or vaccinated against, measles. The specific aims of the project are: (1) to test whether direct killing by CD8 + CTL occurs in the acute phase of measles and to determine to which of 3 measles antigens, the hemagglutinin (HA), the fusion (F) or the nucleoprotein (NP), this type of immunity is directed. To achieve this aim recombinant vaccinia/measles viruses expressing these proteins will be used to infect B cell targets matched by HLA class l locus of the donor and tested in cytotoxicity assays. (2) to test whether recombinant attenuated vaccinia/measles viruses and canary pox/measles recombinants, which are candidates for future measles vaccines, can be used to recall CTL in children who have recently been infected with measles and in children vaccinated against measles. To achieve this aim, these non-replicating virus vectors will be used to infect autologous mononuclear cells in order to stimulate CTL to kill autologous B cell targets infected with measles virus. Use of anti CD4 and anti CD8 antibody will define which type of cell effects killing. (3) to test, using methods described in 1 and 2, whether exposure to natural measles boosts CTL responses in mothers immune to measles and in siblings vaccinated against measles. (4) to identify the peptide epitopes contained in the HA, F and NP antigens of the Edmonston and local strains of measles virus, which are recognized by HLA class 1 restricted CTL common to West Africans. The amino acid sequences of the 3 measles antigens will be examined to predict which will bind to the common West African HLA class 1 motifs and will then be tested in assembly assays using T2 mutant cells transfected with these HLA genes. Those that bind with high affinity will be tested in cytotoxicity assays. Knowledge gained from the above studies will allow decisions as to whether the attenuated measles recombinant viruses are likely to be useful vaccines in West Africa.

该项目的广泛长期目标是获得免疫知识 西非人受细胞毒性T淋巴细胞（CTL）影响的麻疹 感染麻疹或接种麻疹疫苗的。 该委员会的具体目标 （1）检测CD 8 + CTL是否直接杀伤人外周血淋巴细胞， 麻疹的急性期，并确定3种麻疹抗原中的哪一种， 血凝素（HA）、融合蛋白（F）或核蛋白（NP）， 免疫力是定向的。 为了实现这一目标，重组 表达这些蛋白质的牛痘/麻疹病毒将用于感染 B细胞靶标与供体的HLA I类基因座匹配，并在 细胞毒性测定。 (2)检测重组减毒 牛痘/麻疹病毒和金丝雀痘/麻疹重组体， 未来麻疹疫苗的候选人，可用于召回CTL， 最近感染麻疹的儿童和 接种麻疹疫苗。 为了实现这一目标，这些非复制 病毒载体将用于感染自体单核细胞， 刺激CTL杀伤麻疹感染的自体B细胞靶 病毒 使用抗CD 4和抗CD 8抗体将确定哪种类型的 细胞杀伤效应。 (3)为了测试，使用1和2中描述的方法， 暴露于天然麻疹是否能增强免疫母亲的CTL应答 麻疹和接种麻疹疫苗的兄弟姐妹。 (4)以识别 所述抗体的HA、F和NP抗原中含有的肽表位 Edmonston和当地麻疹病毒株，其被HLA识别 西非常见的1类限制性CTL。 的氨基酸序列 将检查3种麻疹抗原中的哪一种，以预测哪一种将结合到 西非常见的HLA 1类基序，然后将在 使用用这些HLA基因转染的T2突变细胞进行组装测定。 以高亲和力结合的那些将在细胞毒性测定中进行测试。 从上述研究中获得的知识将有助于决定是否 减毒的麻疹重组病毒可能是有用的 西非的疫苗。