Therap Human Monoclonal Antibod for Treatment of Hantavirus Cardiopulmonary Syndr

在美洲，尚未开发出预防HCPS的有效疫苗， 目前仅限于支持性治疗。利巴韦林虽然在体外有效限制病毒复制， 尚未最终证明其在缓解HCPS严重程度方面有效。 最近一项对SNV感染患者的研究表明，轻度疾病与 入院时抗SN病毒中和（Nt）抗体水平较高（>1：800）（13）。 此外，在同一时间点的Nt抗体的低滴度（si：200）与严重疾病相关， 高死亡率。事实上，将来自恢复的HCPS患者的免疫血浆施用给鹿小鼠是可行的。 如果在攻击前施用，足以保护这些储库啮齿动物免受病毒攻击 （Rafael Medina和Brian Hjelle，未发表的数据）。在另一项研究中，ANDV特异性Nt抗体 （从恒河猴中回收）能够保护仓鼠免受致命疾病时，被动 管理（34）这些抗体也能够交叉中和SNV和黑溪运河 病毒（北美的另一种HCPS病毒）。在SNV、汉滩病毒、普马拉病毒的啮齿动物模型中 （PUUV）和首尔病毒感染，母体获得或被动转移的抗体就足够了 预防感染和/或改善疾病（18，21，27，37-39，44，71，72，82）。基于这些 观察，我们假设Nt抗体的被动给药可能是有效的， 治疗干预，以减少/预防由于HCPS疾病导致的发病率和死亡率 感染了SNV和ANDV

An effective vaccine for the prevention of HCPS in the Americas has not been developed and treatment is limited to supportive care at present. Ribavirin, while effective at restricting viral replication in vitro, has not conclusively been shown to be efficacious in alleviating HCPS severity. A recent study of SNV-infected patients demonstrated that mild disease is significantly associated with high levels (>1:800) of anti-SN virus neutralizing (Nt) antibodies at the time of hospital admission(13). Furthermore, low titers (si :200) of Nt antibody at this same time point correlate with severe disease and high mortality. Indeed, administration of immune plasma from recovered HCPS patients to deer mice is sufficient to protect these reservoir rodents from viral challenge if it is administered prior to challenge (Rafael Medina and Brian Hjelle, unpublished data). In a separate study, ANDV-specific Nt antibodies (recovered from Rhesus macaques) were able to protect hamsters from lethal disease when passively administered(34). These antibodies were also able to cross-neutralize both SNV and Black Creek Canal virus (another HCPS agent in North America). In rodent models of SNV, Hantaan virus, Puumala virus (PUUV), and Seoul virus infection, maternally-acquired or passively transferred antibodies are sufficient to prevent infection and/or ameliorate disease(18, 21, 27, 37-39, 44, 71, 72, 82). Based upon these observations, we hypothesize that passive administration of Nt antibodies may be an effective therapeutic intervention to reduce/prevent morbidity and mortality due to HCPS disease resulting from infection with SNV and ANDV.