Immunodominant epitopes of a smallpox vaccine in humans

描述(申请人提供)：天花疾病的顶峰和1977年从人类人口中根除天花发生在免疫学和分子生物学的现代时代之前。因此，关于天花康复的免疫相关因素或巴氏杆菌病毒表达的交叉反应蛋白是其作为天花疫苗成功的原因，人们知之甚少。唯一与预防严重天花相关的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。作为一项全面、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2.09亿剂新的组织培养天花疫苗。此外，正在考虑下一代天花疫苗的提议，这种疫苗将具有更高的安全性，减少与疫苗相关的并发症，特别是在免疫抑制的个人中。 如果不详细了解在根除天花计划中被证明有效的疫苗的免疫原性，评估新的Acambis和Baxter疫苗或其他安全性增强的第二代疫苗的效力将是有问题的。对人类B和T细胞对痘苗病毒编码蛋白的免疫反应的详细研究将有助于填补这一知识空白，还可能确定中和、补体结合或ADCC(抗体依赖细胞细胞毒)抗体的靶标，这可能有助于开发有效的VIG替代品。 我们建议在志愿者接种Dryvax疫苗期间，确定由B和T细胞反应识别的痘苗病毒编码蛋白的特征。具体目标是： 1.鉴定对免疫优势痘苗病毒蛋白的抗体反应，以及 2.鉴定具有代表性的痘苗病毒特异性T细胞克隆的表位特异性。

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.