Protection against Bordetella pertussis transmission conferred by established and novel vaccines

总结： 目前的疫苗未能预防百日咳杆菌的持续传播， 它的复兴背后的核心问题，并被CDC和NIH列为优先考虑的问题， 新兴病原体临床研究和狒狒实验已经证实， 无细胞疫苗可预防疾病，但不能防止定植、脱落和 B的传播。百日咳。不幸的是，这些实验系统并不实用，或者 甚至可以用于必要的研究，以开发可以预防的改进疫苗， 定植、脱落和传播。我们最近发现并克服了 允许B的障碍。百日咳菌有效地定殖小鼠，这使我们能够开发 用于小鼠之间的定殖、脱落和传播的测定。我们还开发了 创新的外膜囊泡（OMV）为基础的疫苗，并表明他们限制， 这是对现有疫苗的重大改进。在这里，我们将使用我们的新 开发了测定方法来确定当前和我们的新型疫苗对B能力的影响。 百日咳有效地定殖动物，被排放到他们的环境和传播到新的 hosts.然后，我们将定义和比较与以下疾病相关的全身免疫反应： 通过与阻断相关的粘膜免疫应答保护免受疾病 定植、脱落和传播。这些实验将共同证明 这些新的检测方法可能会彻底改变开发和测试新的 疫苗和治疗。他们还可能验证基于OMV的 疫苗，并提出证据表明，这种新的疫苗可以克服的主要失败， 通过阻断其传播，提供了希望， 这个国家卫生研究院和疾控中心的优先代理人

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.