Immunogenetics of Smallpox Vaccination

天花疫苗接种的免疫遗传学

• 批准号: 7641580
• 负责人: SAMUEL L. STANLEY
• 金额: $ 31.99万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7641580
• 关键词: Acute; Adult; Adverse effects; Adverse reactions; Alleles; Animal Model; Atopic Dermatitis; Blood; Candidate Disease Gene; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Research; Communicable Diseases; Coupled; Data; Dermatitis; Detection; Development; Diagnosis; Disease; Distal; Doctor of Medicine; Eczema; Eczema Vaccinatum; Elements; Enlargement of lymph nodes; Ensure; Exanthema; Experimental Designs; Family member; Fever; Fibrinogen; Foundations; Frequencies; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Haplotypes; Health Personnel; Human; Immune; Immune response; Immunization; Immunogenetics; Immunologics; Individual; Infection; Inflammatory Response; Interleukin-10; Interleukin-4; Lead; Link; Lymphatic Diseases; Methods; Myalgia; Orthopoxvirus; Outcome; Pharmaceutical Preparations; Pharmacogenetics; Play; Population; Poxviridae; Poxviridae Infections; Predisposition; Prevalence; Prospective Studies; Protocols documentation; Recontacts; Relative (related person); Research Design; Resistance; Retrospective Studies; Risk; Risk Factors; Role; Sample Size; Screening procedure; Secondary to; Single Nucleotide Polymorphism; Site; Smallpox; Smallpox Vaccine; Source; Strategic Planning; Symptoms; Syndrome; Temperature; Testing; Time; Training; Vaccinated; Vaccination; Vaccines; Vaccinia; Variant; Virus; Virus Diseases; Virus Shedding; Volunteer Group; base; emergency service responder; insight; mortality; novel vaccines; prevent; receptor; response; volunteer

The goal of this project is to identify genes that are involved in susceptibility and resistance to human vaccinia infection, and, consequently, in some of the adverse effects seen with smallpox vaccination. We (R.B.B.) recently led a multi-center prospective study on the clinical response to vaccinia immunization in 680 na'l've individuals. Among the 665 individuals responding to the vaccine, 84 (13%) developed fever, muscle aches and lymphadenopathy giving rise to what we have called Acute Vaccinia Syndrome (AVS) in approximately 30% of vaccines. The timing of the onset of these symptoms matched the timing of the highest levels of viral shedding, indicating that fever, and the other components of AVS appear to be secondary to the virus. We hypothesize that individuals developing AVS (and especially fever) have disease-predisposing alleles that are associated with abnormal innate immune or delayed adaptive immune responses to vaccinia. These individuals may be more susceptible to poxviruses in general, and could constitute a group at increased risk for mortality if exposed to smallpox. We propose to identify genes that are expressed in response to vaccinia infection at the site of inoculation and systemically using a transcriptional analysis. We will compare responses between individuals that develop AVS, and those individuals who develop no adverse reactions to immunization. These studies will provide us with a transcriptional profile of the host response to vaccinia infection, identify key molecules in the host response, and, establish parameters for protective immune responses that could be used to test the efficacy of new vaccines. We will also identify alleles associated with adverse effects to vaccinia immunization and abnormal innate immune responses to the virus through the analysis of haplotypes based on single nucleotide polymorphisms in candidate genes. The identify of these alleles may provide clues to the critical elements of the host response to poxvirus, and could provide a method to identify individuals at increased risk for adverse effects to the vaccine, or more severe disease with poxvirus infection. The design of the study, with the inclusion of transcriptional profiling of individuals receiving vaccinia immunization coupled with a detailed virologic and immunologic profile, ensures that we will obtain valuable information on the host response to vaccinia immunization.

该项目的目标是鉴定与易感性和抗性相关的基因 人类痘苗感染，以及因此导致的天花疫苗接种带来的一些不良影响。 我们（R.B.B.）最近领导了一项关于痘苗免疫临床反应的多中心前瞻性研究 第 680 章在对疫苗有反应的 665 人中，84 人（13%）出现发烧， 肌肉疼痛和淋巴结肿大导致我们所说的急性痘苗综合症（AVS） 大约30%的疫苗。这些症状出现的时间与 病毒脱落水平最高，表明发烧，而 AVS 的其他成分似乎是 继发于病毒。我们假设患有 AVS（尤其是发烧）的个体有 与先天免疫异常或延迟适应性免疫相关的疾病诱发等位基因 对牛痘的反应。一般来说，这些人可能更容易感染痘病毒，并且可能 构成如果接触天花则死亡风险增加的群体。我们建议鉴定基因 在接种部位表达对痘苗感染的反应，并系统地使用 转录分析。我们将比较发生 AVS 的个体和那些患有 AVS 的个体之间的反应 对免疫接种没有产生不良反应的人。这些研究将为我们提供 宿主对痘苗感染反应的转录谱，识别宿主反应中的关键分子， 并且建立保护性免疫反应的参数，可用于测试新药物的功效 疫苗。我们还将确定与痘苗免疫不良反应相关的等位基因和 通过基于单一的单倍型分析来发现对病毒的异常先天免疫反应 候选基因的核苷酸多态性。这些等位基因的鉴定可能为关键的线索提供线索 宿主对痘病毒反应的要素，并可以提供一种方法来识别个体 对疫苗产生不良影响或因痘病毒感染而患上更严重疾病的风险。的设计 研究，包括接受牛痘疫苗接种的个体的转录谱分析 具有详细的病毒学和免疫学特征，确保我们获得有关宿主的有价值的信息 对痘苗免疫的反应。