Vaccinia Virus Antibody Kinetics and Residual Immunity

痘苗病毒抗体动力学和残余免疫

• 批准号: 7122929
• 负责人: STEVEN J. LAWRENCE
• 金额: $ 10.57万
• 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 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7122929
• 关键词: Poxviridae; Poxviridae disease; active immunization; antibody titering; antigen antibody reaction; bioterrorism /chemical warfare; clinical research; drug screening /evaluation; emerging infectious disease; enzyme linked immunosorbent assay; human population study; human subject; neutralizing antibody; patient oriented research; serology /serodiagnosis; smallpox vaccine; smallpox virus; vaccine evaluation; vaccinia virus; virus antigen; virus diseases; virus envelope; virus protein

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成为独立的临床研究者。该候选人已完成传染病专科培训和流行病学研究生学习，正在寻求进一步的导师指导培训，以实现既定的职业目标。总体职业目标是开发一个以患者为导向的研究计划，调查与疫苗相关的宿主对生物恐怖主义相关和新出现的病毒感染的免疫力，同时成为一名成功的独立临床医生研究员。拟议的职业发展计划包括提供先进免疫学和生物统计学培训的教学培训，以及圣路易斯大学疫苗开发中心和华盛顿大学医学院合作进行的指导研究。拟议研究部分的目标是将新的免疫学发现转化为评估疫苗相关宿主对痘病毒免疫的临床研究的设计和实施。 该研究的具体目的是：确定痘苗病毒疫苗接种后特异性抗痘苗病毒包膜蛋白抗体的动力学，并与天花免疫力相关。 估计特定人群中的天花群体免疫力。 第一个目标将通过使用酶联免疫吸附测定 (ELISA) 来表征最近接种改良痘苗安卡拉 (MVA) 和 Dryvax 的个体对特定痘苗病毒包膜蛋白 B5R、A33R、L1R 和 A27L 的抗体反应来实现(r) 疫苗。通过与全病毒抗痘苗抗体滴度、中和抗体滴度以及 Dryvax(r) 接受者的主要皮肤反应的存在进行比较，特异性抗体反应将与天花免疫力相关联。第二个目标将通过在中西部大都市区进行基于人群的血清学调查来实现，以估计与免疫力相关的抗体滴度的流行率。根据这些结果将估计天花群体免疫力。预计这些结果将增加有关痘苗病毒免疫产生的天花免疫力的知识体系，并提供正常人类对特定痘苗包膜蛋白（潜在的亚单位疫苗候选物）反应的基线。