Protection against Bordetella pertussis transmission conferred by established and novel vaccines

现有疫苗和新型疫苗可预防百日咳博德特氏菌传播

基本信息

批准号：
10194677
负责人：
Eric T Harvill
金额：
$ 22.65万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-19 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10194677
关键词：
Acellular Vaccines Address Adverse reactions Affect Animal Model Animals Antibody Response Antigens Biological Assay Blood Bordetella pertussis Cells Centers for Disease Control and Prevention (U.S.)Clinical Research Data Development Disease Dose Environment Failure Formulation Gold Immune Immune response Immunity Immunization Immunoglobulin A Immunologics Infection Inflammation Interruption Intranasal Administration Location Lower respiratory tract structure Lung Measures Mediating Membrane Modeling Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mucous body substance Mus Nasal cavity Nasopharynx Newborn Infant Nose Papio Patients Pertussis Pertussis Vaccine Phase Population Process Production Proteins Publishing Research Respiratory System Route System T-Lymphocyte Testing Time Trachea United States National Institutes of Health Vaccinated Vaccination Vaccines Vesicle base design emerging pathogen experimental study immune function improved innovation lung colonization mouse model next generation novel novel vaccines prevent response transmission process vaccine candidate vaccine development vaccine-induced antibodies

项目摘要

SUMMARY: The failures of current vaccines to prevent the ongoing transmission of Bordetella pertussis is the central problem behind its resurgence and listing by both CDC and NIH as a priority re- emerging pathogen. Clinical studies and baboon experiments have confirmed that current acellular vaccines protect against disease but fail to prevent colonization, shedding and transmission of B. pertussis. Unfortunately, these experimental systems are not practical, or even available, for the necessary research to develop improved vaccines that can prevent colonization, shedding and transmission. We recently discovered and have overcome prior obstacles to allowing B. pertussis to efficiently colonize mice which has allowed us to develop assays for colonization, shedding and transmission between mice. We have also developed innovative outer membrane vesicle (OMV)- based vaccines and shown that they limit colonization, a substantial improvement over current vaccines. Here we will use our newly developed assays to define the effects of current and our novel vaccines on the ability of B. pertussis to efficiently colonize animals, be shed into their environment and transmit to new hosts. We will then define and compare the systemic immune responses associated with protection from disease with the mucosal immune responses associated with blocking colonization, shedding and transmission. Together these experiments will demonstrate the use of these new assays that are likely to revolutionize approaches to develop and test new vaccines and treatments. They are also likely to validate the improved efficacy of OMV-based vaccines and present evidence that such new vaccines can overcome the major failure of current vaccines by blocking its transmission, providing hope that we could actually eradicate this NIH and CDC priority agent.

概括：当前的疫苗阻止Bordetella百日咳持续传播的失败是 CDC和NIH的复兴和上市背后的主要问题作为重点新兴病原体。临床研究和狒狒实验证实了当前细胞疫苗预防疾病，但无法防止定殖，脱落和百日咳B.的传播。不幸的是，这些实验系统不实用，或者甚至可用，为了进行必要的研究，以开发改进的疫苗，以防止殖民，脱落和传播。我们最近发现并克服了先验允许百日咳B.百日咳有效地定居小鼠的障碍，这使我们得以发展小鼠之间定植，脱落和传播的测定。我们也发展了创新的外膜囊泡（OMV） - 基于疫苗，并表明它们限制了定植，比目前的疫苗有很大的改善。在这里，我们将使用新的开发的测定方法来定义当前和我们的新疫苗对B的影响。百日咳有效地定居动物，脱落到它们的环境中并传播到新的环境主持人。然后，我们将定义和比较与防止与阻塞相关的粘膜免疫反应的疾病殖民，脱落和传播。这些实验将共同证明使用在这些新测定中可能会彻底改变开发和测试新的方法疫苗和治疗。他们还可能验证基于OMV的提高功效疫苗和证据表明，这种新疫苗可以克服当前的疫苗通过阻止其传输，提供希望我们可以真正消除的希望该NIH和CDC优先级代理。