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

• 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
• 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

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爆发的频率和影响都在增加。随着天气模式的演变，啮齿动物 在与人类接触增加导致感染的地区，人口受到影响，并可能成倍增加。 汉坦病毒，包括安第斯山脉（ANDV）和辛农布尔（SNV），通过感染者的排泄物传播。 啮齿类动物，并在雾化时感染人类。在美洲，汉坦病毒感染导致汉坦病毒 心肺综合征（HCPS），一种以肺水肿快速发作为特征的破坏性疾病， 呼吸衰竭和心源性休克。治疗是支持性的，而不是针对病原体的，因此， 大约40%的患者无法存活。因为汉坦病毒建立终身，无症状 感染的啮齿动物水库，他们是非常普遍的性质，并代表了一个不断的威胁， 人类例如，SNV由北美最丰富的哺乳动物鹿鼠携带， 在美国和加拿大几乎无处不在。在南美洲ANDV的情况下， 除了啮齿动物到人的传播外，还会发生人到人的传播，不仅使患者， 而且家庭成员和医护人员也处于危险之中。尽管这种感染的可能性很大， 由于病死率高，没有FDA批准的治疗方案或疫苗可用。因此，汉坦病毒 被列为NIAID优先病原体，并被认为是潜在的生物恐怖主义威胁。我们的长期目标是 开发一种有效的治疗方法来对抗引起HCPS的汉坦病毒。 该提案寻求开发用于治疗性和/或预防性治疗以下疾病的人中和抗体： 由ANDV引起的HCPS。我们已经组建了一个多学科的团队，包括分子病毒学家，临床医生， 具有开发抗体疗法经验的行业合作伙伴。研制成功 抗ANDV的有效中和抗体有可能成为治疗的一线抗病毒药物，或 预防HCPS。