Vaccinia Virus Antibody Kinetics and Residual Immunity

痘苗病毒抗体动力学和残余免疫

• 批准号: 7487443
• 负责人: STEVEN J. LAWRENCE
• 金额: $ 11.25万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487443
• 关键词: Address; Adverse effects; Animal Model; Antibodies; Antibody Formation; Antigens; Area; Attenuated; Biological Assay; Biometry; Bioterrorism; Clinical Investigator; Clinical Research; Communicable Diseases; Cutaneous; Development; Development Plans; Enzyme-Linked Immunosorbent Assay; Epidemiology; Goals; Gold; Herd Immunity; Human; Immune response; Immunity; Immunization; Immunology; Individual; Investigation; Kinetics; Knowledge; Lesion; Licensing; Life; Measures; Mentors; Modified Vaccinia Virus Ankara; Orthopoxvirus; Population; Poxviridae; Prevalence; Principal Investigator; Proteins; Purpose; Reaction; Relative (related person); Research; Research Personnel; Residual state; Role; Saints; Scientific Advances and Accomplishments; Serological; Smallpox; Smallpox Vaccine; Standards of Weights and Measures; Structure; Subunit Vaccines; Surrogate Markers; Surveys; Training; Translating; Treatment Protocols; Universities; Vaccinated; Vaccination; Vaccines; Vaccinia; Vaccinia Vaccine; Vaccinia virus; Virus; Virus Diseases; Washington; base; career; design; env Gene Products; insight; interest; medical schools; metropolitan; neutralizing antibody; novel; patient oriented; patient oriented research; programs; response; vaccine development; virus envelope

DESCRIPTION (provided by applicant): The purpose of this application is to facilitate the development of the candidate into an independent clinical investigator. The candidate has completed infectious diseases subspecialty training and epidemiology graduate studies and is seeking further mentor-guided training to attain the stated career goals. The overarching career goal is to develop a patient-oriented research program investigating vaccine-related host immunity to bioterrorism-associated and emerging viral infections, while becoming a successful independent clinician-researcher. The proposed career development plan consists of didactic training that will provide advanced immunology and biostatistics training, and mentored research to be conducted as a collaborative effort between Saint Louis University's Center for Vaccine Development and Washington University School of Medicine. The goal of the proposed research component is to translate novel immunology findings into the design and implementation of clinical studies evaluating vaccine-related host immunity to poxviruses. The specific aims of the research are: To determine the kinetics of specific anti-vaccinia virus envelope protein antibodies post vaccinia virus vaccination and to correlate with smallpox immunity. To estimate smallpox herd immunity in a defined population. The first aim will be accomplished by using an enzyme-linked immunosorbent assay (ELISA) to characterize the antibody responses to the specific vaccinia virus envelope proteins B5R, A33R, L1R, and A27L in individuals recently vaccinated with Modified Vaccinia Ankara (MVA) and Dryvax(r) vaccines. The specific antibody responses will be correlated to smallpox immunity by comparison to whole virus anti-vaccinia antibody titers, neutralizing antibody titers, and for Dryvax(r) recipients, presence of a major cutaneous reaction. The second aim will be accomplished by performing a population-based serological survey in a midwestern metropolitan area to estimate the prevalence of antibody titers that are correlated with immunity. From these results smallpox herd immunity will be estimated. The results are expected to add to the body of knowledge regarding smallpox immunity generated by vaccinia virus immunization and to provide a baseline of normal human responses to specific vaccinia envelope proteins that are potential subunit vaccine candidates.

描述（由申请人提供）：本申请的目的是促进候选人发展为独立的临床研究者。该候选人已经完成了传染病的培训和流行病学研究生研究，并正在寻求进一步的导师指导培训以实现既定的职业目标。总体职业目标是制定以患者为导向的研究计划，研究与疫苗相关的宿主免疫，以对生物恐怖相关和新兴的病毒感染，同时成为成功的独立临床医生研究者。拟议的职业发展计划由教学培训组成，该培训将提供先进的免疫学和生物统计学培训，并指导研究，作为圣路易斯大学疫苗开发中心与华盛顿大学医学院之间的合作努力。拟议的研究组成部分的目的是将新颖的免疫学发现转化为评估与疫苗相关宿主对痘病毒的免疫的临床研究的设计和实施。 这项研究的具体目的是：确定疫苗病毒疫苗接种后特定抗Vaccinia病毒包膜蛋白抗体的动力学，并与天花免疫相关。 估计在定义的人口中的天花群免疫。 第一个目标将通过使用酶联免疫吸附测定法（ELISA）来表征对最近在用改良的vacinia ankara ankara（Mva）和Drulvax（R）疫苗接种的个体中对个体中对个体中的抗体反应B5R，A33R，L1R和A27L。通过与整个病毒抗Vaccinia抗体滴度，中和抗体滴度和Dryvax（R）受体相比，特异性抗体反应将与天花免疫相关。第二个目标将通过在中西部都会区进行基于人群的血清学调查来估计与免疫相关的抗体滴度的流行。通过这些结果，将估计天花群的免疫力。预计该结果将增加有关疫苗病毒免疫产生的天花免疫力的知识，并提供对特定疫苗包膜蛋白的正常反应的基线，这些蛋白质是潜在的亚基疫苗候选物。