Development of a vaccine to prevent Pneumocystis pneumonia

开发预防肺孢子虫肺炎的疫苗

• 批准号: 9906567
• 负责人: MICHAEL Robert DOWNES
• 金额: $ 27.24万
• 依托单位: NXT BIOLOGICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906567
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adverse reactions; Aging; Amino Acids; Antibody titer measurement; Antifungal Agents; B-Lymphocytes; Biology; Cancer Patient; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Development; Diagnosis; Disease; Drug resistance; Experimental Models; Formulation; Frequencies; Fungal Vaccines; Genomics; Goals; HIV; HIV Infections; HIV diagnosis; Human; Immune response; Immune system; Immunity; Immunization; Immunocompromised Host; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Immunologic Memory; Immunologics; Immunosuppression; Immunotherapeutic agent; Immunotherapy; In Vitro; Incidence; Individual; Infection; Inflammatory; Inflammatory Response; Life; Lung; Macaca; Memory; Modeling; Morbidity - disease rate; Obstructive Lung Diseases; Opportunistic Infections; Organ Transplantation; Organism; Pathogenesis; Persons; Phase; Plasma; Pneumocystis; Pneumocystis carinii; Pneumocystis carinii Pneumonia; Population; Populations at Risk; Preparation; Prevention; Primates; Production; Prophylactic treatment; Prospective Studies; Protein Subunits; Proteins; Recombinants; Reporting; Research; Resources; Risk; SIV; Specificity; Testing; Therapeutic Uses; Therapeutic immunosuppression; Time; Tissues; Transplant Recipients; Treatment Failure; Trimethoprim-Sulfamethoxazole; Vaccinated; Vaccine Therapy; Vaccines; Virus Diseases; Work; antiretroviral therapy; base; commercialization; disorder control; experience; immunogenicity; immunosuppressed; lead optimization; mortality; natural antibodies; nonhuman primate; novel; pathogen; patient population; prevent; prophylactic; protective efficacy; public health relevance; recombinant peptide; research clinical testing; response; seropositive; standard care; treatment guidelines; vaccination strategy; vaccine candidate; vaccine development; vaccine evaluation

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.

尽管真菌性疾病是日益增加的临床负担，特别是在 对于免疫功能低下的患者，没有抗真菌疫苗被批准用于临床使用。真菌 耶氏肺孢子虫是机会致病菌，是肺孢子虫肺炎（PCP）的病原体， 它仍然是一种严重的艾滋病定义的机会性感染， 接受免疫抑制治疗的患者，包括器官移植受者、癌症患者、 炎症性疾病和由于衰老、先天性或 获得性免疫抑制状态除了导致PCP，一些研究表明， 在HIV感染者和非HIV感染者中，Pc定植与慢性阻塞性肺疾病（COPD）之间的关系 感染人群。这些患者人群中的每一个都将受益于预防性PCP疫苗 在免疫抑制之前（例如，在免疫疗法的临床过程之前）或在免疫抑制之后（例如，在免疫疗法的临床过程之前）施用。 有感染艾滋病毒风险的人群或诊断为艾滋病毒感染时的个人。的总目标 这项研究旨在开发一种疫苗，用于预防HIV+和其他感染者的PCP和相关肺部后遗症。 免疫力低下的人群。为此，我们已经确定并开发了一种候选疫苗， 基于肺孢子虫的蛋白质kexin我们已经生产了一种基于肺孢子虫的候选疫苗 蛋白质，kexin，并表明，免疫非人灵长类动物（NHP）之前，猿免疫缺陷 病毒（SIV）感染诱导高水平，kexin特异性血浆和肺免疫球蛋白滴度， 对抗肺孢子虫肺炎第一阶段申请的目标是完成以下潜在客户的优化： 通过测试耶氏肺孢子虫衍生的可欣蛋白衍生物的免疫原性来测试疫苗。我们 将评估NHP在免疫接种后的免疫应答，并用重组Jirovecii疟原虫加强免疫 肽的SIV感染的猕猴，并将评估特定的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，我们将集中精力 临床试验用疫苗的制备和评价。