Development of a vaccine to prevent Pneumocystis pneumonia

开发预防肺孢子虫肺炎的疫苗

基本信息

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
项目类别：
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

项目摘要

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.

尽管真菌疾病是临床负担的增加，尤其是在免疫功能低下的患者，没有批准用于临床用途的抗真菌疫苗。真菌机会性病原体，肺炎藻氏菌是肺炎肺炎（PCP），这仍然是一种严重的辅助，机会性感染，并且对人的关注程度越来越大接受免疫抑制疗法，包括器官移植受者，癌症患者，患有炎症性疾病以及由于老化，先天性或获得了免疫抑制状态。除了引起PCP外，几项研究表明在HIV感染和非HIV中，PC定植和慢性阻塞性肺疾病（COPD）之间感染人群。这些患者种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，在接受免疫疗法的临床过程之前）或在诊断出HIV感染时患HIV感染或患者的风险。总体目标这项研究是开发用于预防pcp和相关肺后遗症的疫苗免疫功能低下的人群。为此，我们已经确定并开发了候选疫苗基于气囊蛋白Kexin。我们已经基于肺结囊生产了疫苗候选者蛋白质，Kexin，并表明在邻肌免疫缺陷之前对非人类灵长类动物的免疫接种（NHP）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并保护针对肺炎肺炎肺炎。该阶段I应用的目的是完成对通过测试肺炎刺激的jirovecii衍生的Kexin蛋白衍生物的免疫原性来进行疫苗。我们将评估免疫后NHP中的免疫反应，并用P. jirovecii重组增强 SIV感染的猕猴中的肽，并将评估特定内存响应的持续时间和质量在免疫抑制状态。随着本概念研究证明的完成，我们将重点放在疫苗进行临床试验的准备和评估。