Protection against Bordetella pertussis transmission conferred by established and novel vaccines

摘要： 目前的疫苗未能阻止百日咳杆菌的持续传播 它复兴并被疾控中心和美国国立卫生研究院列为优先事项背后的核心问题是 新出现的病原体。临床研究和狒狒实验已经证实，目前 无细胞疫苗可预防疾病，但不能防止定植、脱落和 百日咳杆菌的传播。不幸的是，这些实验系统并不实用，或者 即使可用于必要的研究，以开发改进的疫苗，可以预防 殖民、脱落和传播。我们最近发现并克服了之前的 阻碍百日咳杆菌有效地定植小鼠，这使得我们能够 小鼠间定植、脱落和传播的检测。我们还开发了 创新的外膜囊泡(OMV)疫苗，并表明它们限制了 与目前的疫苗相比，这是一项实质性的改进。在这里，我们将使用我们的新 开发了确定当前和我们的新型疫苗对B组疫苗能力的影响的方法。 百日咳能有效地在动物身上定植，进入它们的环境，并传播给新的 主持人。然后，我们将定义和比较与以下相关的系统免疫反应 与阻断相关的粘膜免疫反应对疾病的保护 殖民、脱落和传播。这些实验将一起演示如何使用 这些新的分析方法可能会革命性地开发和测试新的 疫苗和治疗。他们还可能验证基于OMV的改进的疗效 疫苗，并提供证据表明，这种新疫苗可以克服重大失败 目前的疫苗通过阻止其传播，提供了我们实际上可以根除的希望 美国国立卫生研究院和疾病预防控制中心的优先特工。

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.