A human monoclonal antibody therapy for treatment of hantavirus cardiopulmonary syndrome

一种治疗汉坦病毒心肺综合征的人单克隆抗体疗法

基本信息

批准号：
10611715
负责人：
Jason W. Botten
金额：
$ 100万
依托单位：
CELDARA MEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-08 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10611715
关键词：
Academia Acute Advanced Development Affect Americas Andes Virus Animals Antibodies Antibody Therapy Antiviral Agents Area Argentina B-Lymphocytes Bioterrorism Canada Cardiogenic Shock Cardiopulmonary Case Fatality Rates Category A pathogen Classification Clinical Collaborations Deer Mouse Development Disease Disease Outbreaks Dose Ebola virus FDA approved Family Family health status Family member Fatality rate Frequencies Glycoproteins Goals Government Hamsters Hantavirus Hantavirus Infections Health Personnel Human Immune Immune Plasma Immune Sera Immunize Immunologist Industry Infection Mammals Maps Mesocricetus auratus Modeling Molecular Monoclonal Antibodies Monoclonal Antibody Therapy Mus National Institute of Allergy and Infectious Disease Nature North America Patients Pharmaceutical Preparations Phase Plasmablast Population Preparation Prevention Prophylactic treatment Pulmonary Edema Research Respiratory Failure Risk Rodent Security Sin Nombre virus Small Business Technology Transfer Research South American Specificity Syndrome Technology Therapeutic Therapeutic antibodies Tissues Toxic effect Vaccines Viral Virus Work aerosolized biosecurity candidate selection clinical development cross reactivity experience future pandemic human monoclonal antibodies in vivo industry partner infected vector rodent manufacturability manufacture multidisciplinary neutralizing antibody neutralizing monoclonal antibodies pandemic disease pandemic potential preclinical development prevent priority pathogen therapeutically effective transmission process vaccine access viral outbreak weather patterns

项目摘要

PROJECT SUMMARY Rodent-borne viral outbreaks are increasing in both frequency and impact. As weather patterns evolve, rodent populations are affected and may multiply in areas where increased contact with humans results in infection. Hantaviruses, including Andes (ANDV) and Sin Nombre (SNV), are transmitted through the excreta of infected rodents and, when aerosolized, infect humans. In the Americas, hantavirus infection leads to hantavirus cardiopulmonary syndrome (HCPS), a devastating condition that features rapid onset of pulmonary edema, respiratory failure and cardiogenic shock. Treatment is supportive, not pathogen-targeted, and accordingly, approximately 40% of patients do not survive. Because hantaviruses establish lifelong, asymptomatic infections in their rodent reservoirs, they are highly prevalent in nature and represent a constant threat to humans. For example, SNV is carried by the most abundant mammal in North America, the deer mouse, which has a near ubiquitous distribution throughout the US and Canada. In the case of the South American ANDV, in addition to rodent-to-human transmission, human-to-human transmission occurs, putting not only the patient, but also family members and health care workers at risk. Despite this large potential for infection and the high case fatality rate, there are no FDA-approved treatment options or vaccines available. Hantaviruses are thus classified as NIAID Priority Pathogens and considered potential bioterrorism threats. Our long term goal is to develop an effective therapeutic against HCPS-causing hantaviruses. This proposal seeks to develop human neutralizing antibodies for therapeutic and/or prophylactic treatment of HCPS caused by ANDV. We have assembled a multidisciplinary team of molecular virologists, clinicians, and industry partners with experience developing antibody-based therapeutics. The successful development of a potent neutralizing antibody against ANDV has the potential to be a first-line antiviral for the treatment or prevention of HCPS.

项目摘要啮齿动物传播的病毒暴发在频率和影响方面都在增加。随着天气模式的发展，啮齿人口受到影响，可能会在与人类接触增加的地区繁殖导致感染。汉坦病毒，包括安第斯山脉（ANDV）和罪恶Nombre（SNV），通过感染的排泄传播啮齿动物，当雾化后，会感染人类。在美洲，汉塔病毒感染导致汉坦病毒心肺综合征（HCP），一种毁灭性疾病，具有肺水肿的快速发作，呼吸衰竭和心源性休克。治疗是支持性的，而不是病原体的靶向，因此大约40％的患者无法生存。因为汉坦病毒建立终身，无症状在啮齿动物的储层中感染，它们在本质上非常普遍，并代表着对人类。例如，SNV是由北美最丰富的哺乳动物携带的在美国和加拿大的分布几乎无处不在。就南美和南美洲而言除了啮齿动物到人类的传播外，还会发生人类到人类传播，不仅使患者，而且家庭成员和卫生保健工作者处于危险之中。尽管感染了很大的潜力和高病例死亡率，没有FDA批准的治疗方案或疫苗可用。因此，汉坦病毒是归类为NIAID优先病原体，并认为潜在的生物恐怖威胁。我们的长期目标是针对引起HCPS的汉坦病毒开发有效的治疗方法。该提案旨在开发人类中和抗体的治疗和/或预防治疗的抗体由ANDV引起的HCP。我们组建了一个分子病毒学家，临床医生和具有开发基于抗体的治疗剂的经验的行业合作伙伴。成功发展对ANDV的有效中和抗体具有治疗或预防HCP。