Immunodominant epitopes of a smallpox vaccine in humans

人类天花疫苗的免疫显性表位

• 批准号: 6562346
• 负责人: Robert MARK Buller
• 金额: $ 21.23万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6562346
• 关键词: B lymphocyte; Poxviridae disease; T lymphocyte; antibody formation; bioterrorism /chemical warfare; clinical research; human subject; laboratory mouse; leukocyte activation /transformation; microorganism immunology; smallpox virus; vaccinia virus; viral vaccines; virus antigen; virus protein

DESCRIPTION (provided by applicant): The zenith of the disease smallpox and its eradication in 1977 from human populations occurred prior to the modern era of immunology and molecular biology. Consequently there is little knowledge concerning the immune correlates for recovery from smallpox or the cross-reactive proteins expressed by baccinia virus that were responsible for its success as the smallpox vaccine. The only vaccination indicator that correlated with protection from severe smallpox was the scar. In response to the threat of bioterrorism, the U.S. government has redoubled its efforts to provide strategies that will protect the American public from an outbreak of smallpox or human monkeypox. As part of a comprehensive, multi-faceted plan, the U.S. government has contracted with Acambis Inc. and Baxter Healthcare Corp. to produce approximately 209 million doses of a new tissue culture smallpox vaccine. In addition, proposals are being considered for the next generation of smallpox vaccine that will have an enhanced safety profile, causing fewer vaccine-related complications, especially in immunosuppressed individuals. Evaluating the efficacy of the new Acambis and Baxter vaccine or other second-generation vaccines with enhanced safety profiles will be problematic without detailed knowledge of the immunogenicity of vaccines proven to be efficacious in the smallpox eradication program. Detailed studies on human B and T cell immune responses to proteins encoded by vaccinia virus should help fill this gap in knowledge, and may also identify targets of neutralizing, complement-fixation or ADCC (antibody-dependent cell cytotoxity) antibodies, which may facilitate the development of an efficacious replacement for VIG. We propose to characterize the vaccinia virus-encoded proteins recognized by B and T cell responses during the vaccination of volunteers with the DryVax vaccine. The Specific Aims are to: 1. Characterize the antibody responses to immunodominant vaccinia virus proteins and 2. Identify the epitope specificity of representative vaccinia virus-specific T cell clones.

描述（由申请人提供）：天花疾病的顶峰及其在1977年从人群中根除发生在现代免疫学和分子生物学时代之前。 因此，关于从天花中恢复的免疫相关性或由芽孢杆菌病毒表达的交叉反应蛋白的知识很少，而这些蛋白是其作为天花疫苗成功的原因。 与预防严重天花相关的唯一疫苗接种指标是疤痕。 为了应对生物恐怖主义的威胁，美国政府加倍努力提供战略，以保护美国公众免受天花或人类猴痘的爆发。 作为一项全面、多方面计划的一部分，美国政府已与Acambis Inc.签订合同。和巴克斯特医疗保健公司生产约2.09亿剂新的组织培养天花疫苗。 此外，正在考虑关于下一代天花疫苗的建议，这种疫苗将具有更高的安全性，减少疫苗相关并发症，特别是在免疫抑制的个体中。 如果不详细了解天花根除计划中已证实有效的疫苗的免疫原性，则评价新的Acambis和巴克斯特疫苗或其他安全性增强的第二代疫苗的有效性将是有问题的。 对人类B和T细胞对牛痘病毒编码蛋白的免疫应答的详细研究应该有助于填补这一知识空白，并且还可以确定中和、补体固定或ADCC（抗体依赖性细胞毒性）抗体的靶点，这可能有助于开发VIG的有效替代品。 我们建议表征志愿者接种DryVax疫苗期间B和T细胞应答识别的牛痘病毒编码蛋白。 具体目标是： 1.表征对免疫显性牛痘病毒蛋白的抗体应答， 2.鉴定代表性牛痘病毒特异性T细胞克隆的表位特异性。