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于 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，人们对天花恢复的免疫相关性或牛痘病毒表达的交叉反应蛋白知之甚少，而牛痘病毒是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，提供保护美国公众免受天花或人类猴痘爆发的战略。 作为全面、多方面计划的一部分，美国政府已与 Acambis Inc. 和 Baxter Healthcare Corp. 签订合同，生产约 2.09 亿剂新型组织培养天花疫苗。 此外，正在考虑下一代天花疫苗的提案，该疫苗将具有更高的安全性，减少与疫苗相关的并发症，特别是在免疫抑制个体中。 如果不详细了解在天花根除计划中被证明有效的疫苗的免疫原性，评估新的 Acambis 和 Baxter 疫苗或其他具有增强安全性的第二代疫苗的功效将会出现问题。 对人 B 细胞和 T 细胞对痘苗病毒编码的蛋白质的免疫反应的详细研究应该有助于填补这一知识空白，并且还可能确定中和、补体固定或 ADCC（抗体依赖性细胞毒性）抗体的靶标，这可能有助于开发 VIG 的有效替代品。 我们建议对志愿者接种 DryVax 疫苗期间 B 细胞和 T 细胞反应识别的痘苗病毒编码蛋白进行表征。 具体目标是： 1. 表征对免疫显性痘苗病毒蛋白的抗体反应和 2. 鉴定代表性痘苗病毒特异性 T 细胞克隆的表位特异性。