A human monoclonal antibody therapy for treatment of hantavirus cardiopulmonary syndrome

项目总结 啮齿动物传播的病毒暴发在频率和影响上都在增加。随着天气模式的演变，啮齿动物 人口受到影响，并可能在与人类接触增加导致感染的地区繁殖。 汉坦病毒，包括安第斯病毒(ANDV)和新诺布雷病毒(SNV)，是通过感染者的排泄物传播的 啮齿动物，当被雾化时，会感染人类。在美洲，汉坦病毒感染导致汉坦病毒 心肺综合征(HCPS)，一种破坏性的疾病，其特征是迅速出现肺水肿， 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。因为汉坦病毒建立了终生的，无症状的 在它们的鼠类蓄水池中，它们在自然界中非常普遍，并对 人类。例如，SNV是由北美最丰富的哺乳动物--鹿鼠携带的，它 在美国和加拿大几乎无处不在的分布。在南美ANDV的情况下， 除了啮齿动物在人与人之间的传播外，还会发生人与人之间的传播，不仅使患者， 也包括处于危险中的家庭成员和医护人员。尽管感染的可能性很大，而且 病死率，没有FDA批准的治疗选择或疫苗可用。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由HCPS引起的汉坦病毒。 这项提议寻求开发用于治疗和/或预防性治疗的人中和抗体。 由ANDV引起的HCP。我们已经组建了一个由分子病毒学家、临床医生和 具有开发基于抗体的疗法经验的行业合作伙伴。成功地开发了一种 有效的ANDV中和抗体有可能成为治疗或治疗ANDV的一线抗病毒药物 预防HCPS。

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.