Development of a vaccine to prevent Pneumocystis pneumonia

尽管真菌疾病是越来越大的临床负担，特别是在 对于免疫功能低下的患者，目前还没有获准临床使用的抗真菌疫苗。真菌 条件致病菌--日本肺孢子虫是肺炎(PCP)的病原体， 它仍然是一种严重的定义艾滋病的机会性感染，并日益引起人们的关注 接受免疫抑制治疗，包括器官移植接受者、癌症患者、患有 炎症性疾病和由于年龄、先天性或其他原因而经历自然免疫抑制的人 获得性免疫抑制状态。除了引起PCP外，几项研究还表明两者之间存在关联 HIV感染者和非HIV感染者Pc定植与慢性阻塞性肺疾病(COPD)的关系 受感染的人群。这些患者中的每一个都将受益于预防性的PCP疫苗 在免疫抑制之前(例如，在免疫治疗的临床疗程之前)或在 艾滋病毒感染高危人群或诊断为艾滋病毒感染时的个人。的总目标是 这项研究旨在开发一种疫苗，用于预防HIV+和其他疾病的PCP和相关的肺部后遗症 免疫功能受损的人群。为此，我们已经确定并开发了一种候选疫苗 基于肺孢子虫蛋白，可信。我们已经生产了一种基于肺孢子虫的候选疫苗 蛋白质，可信，并表明在猴免疫缺陷之前免疫非人类灵长类动物(NHP) 病毒(SIV)感染诱导高水平可信特异性血浆和肺免疫球蛋白滴度并保护 抗肺孢子虫肺炎。此第一阶段应用程序的目标是完成Lead优化 通过检测日本肺孢子虫衍生的可信蛋白衍生物对疫苗的免疫原性。我们 将评估免疫后NHP的免疫反应，并用重组P.jiroveciii加强免疫 SIV感染猕猴体内的多肽，并将评估特定记忆反应的持续时间和质量 处于免疫抑制状态。随着这项概念验证研究的完成，我们将致力于 临床试验用疫苗的制备和评价。

Despite the fact that fungal diseases are an increasing clinical burden, particularly among immunocompromised patients, there are no anti-fungal vaccines approved for clinical use. The fungal opportunistic pathogen, Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PCP), which remains a serious AIDS-defining, opportunistic infection and is of increasing concern in persons receiving immunosuppressive therapies, including organ transplant recipients, cancer patients, individuals with inflammatory disease and in persons experiencing natural immunosuppression due to aging, congenital or acquired immunosuppressive states. In addition to causing PCP, several studies have shown an association between Pc colonization and chronic obstructive pulmonary disease (COPD) in both HIV-infected and non-HIV infected populations. Each of these patient populations would benefit from either a prophylactic PCP vaccine administered prior to immunosuppression (for example, prior to a clinical course of immunotherapy) or in populations at risk for HIV infection or individuals at the time of diagnosis of HIV infection. The overall goal of this research is to develop a vaccine for prevention of PCP and related pulmonary sequelae in HIV+ and other immunocompromised populations. Toward this end, we have identified and developed a vaccine candidate based on the Pneumocystis protein, kexin. We have produced a vaccine candidate based on Pneumocystis protein, kexin, and showed that immunization of non-human primates (NHP) prior to simian immunodeficiency virus (SIV) infection induces high level, kexin-specific plasma and lung immunoglobulin titers and protects against Pneumocystis pneumonia. The objective of this Phase I application is to complete lead optimization of the vaccine by testing the immunogenicity of the Pneumocystis jirovecii-derived kexin protein derivative. We will assess the immune response in NHPs following immunization and boost with the P. jiroveciii recombinant peptide in SIV-infected macaques and will evaluate the duration and quality of the specific memory responses in the immunosuppressed state. With the completion of this proof of concept study, we will focus efforts on preparation and evaluation of the vaccine for clinical trial.