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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.

简介: