Passive Immunotherapeutics for Select Agents

暴露后的预防和治疗是管理新出现的病毒感染的重要挑战。 疾病疫苗可能有助于暴露后预防，其中代理人复制s10 wty或最初 被隔离在外围。然而，在大多数情况下，主动免疫并不发生在一个时间帧 其中可以预防或改善疾病。被动免疫疗法具有既定的跟踪记录 狂犬病感染的管理。呼吸道合胞病毒和天花病毒。除了极少数情况 其中抗体与宿主组织交叉反应以引起疾病或增强病毒摄取以加速 随着感染的进展，被动免疫疗法的效果是特异性的。抗病毒药物已与 在许多感染中取得成功，有效化合物的库无疑将得到改善; 尽管如此。被动免疫治疗将继续是一个重要的主要或补充线， 防御被动免疫治疗的试剂包括恢复期血清和单克隆抗体 （MAbs）。单克隆抗体具有确定的反应性和特异性的优点。和增强的安全性。 通过以前在世卫组织实验室网络范围内进行的病原体检测工作， 外周血淋巴细胞（PBL）从恢复与高风险病原体感染的受害者。我们 已经确定PBL可以冷冻储存，并在选择后几个月用于融合， IG生产的轻微损失。该Trans-RCE项目将利用人类PBL并直接与 有效的人杂交瘤融合伴侣细胞系（MFP <$2），以及使用EBV的B细胞永生化 和CpG，然后与HMMA 2.5融合伴侣细胞系进行真核融合，以产生全人单克隆抗体 （fhMAB）对三种选定病原体具有特异性：朱宁病毒、尼帕病毒和Rift。VaHey发烧病毒。的选择 靶点是基于表明被动免疫疗法的潜在治疗作用和可用性的数据。 临床材料的特点。MFP-2的有限评价已在以下背景下进行： 向食品药品管理局递交了一份INO此外，还建立了商业关系，目标是 生产用于治疗非霍奇金淋巴瘤的GMP级fhMAb。这些因素将使过渡 具有抗病毒活性的fhMAbs从动物模型到临床应用。具体目标包括：1.建立 用于筛选恢复期供体血清和人杂交瘤上清液的血清学测定; 2. 表征供体血清和PB 1，并产生人杂交瘤系;和3.测试中和fhMAb用于 动物模型中的保护活性。

Post exposure prophylaxis and treatment are aitical challenges in the management of emerging viral diseases. Vaccines may be helpful in post exposure prophylaxis where agents replicate s10wty or are initially sequestered in the periphery. However, in most instances, active immunity does not occur in a lime frame wherein disease can be prevented or ameliorated. Passive immunotherapy has an established track record in management of infections with rabies. respiratory syncytial, and variola viruses. Except in rare instances where antibodies cross react with host tissues to cause disease or enhance virus uptake to accelerate progression of infection, the effects of passive immunotherapy are specific. Anlivirals have been used with success in many infections, and the repertoire of effective compounds will undoubtedly improve; nonetheless. passive immunotherapy will continue to be a significant primary or complementary line of defense. Reagents for passive immunotherapy include both convalescent serum and monoclonal antibodies (MAbs). MAbs have the advantages of defined reactivity and specificity. and enhanced safety profiles. Through previous work in pathogen detection in context of the WHO laboratory network we have access to peripheral blood lymphocytes (PBL) from victims recovered from infection with high.risk pathogens. We have established that PBL can be stored frozen and used for fusion several months after ootlection with only insignificant loss of Ig production. This Trans-RCE project will exploit human PBL and direct fusion with an effICient human hybridoma fusion partner cell line (MFP¿2), as well as immortalization of B cells using EBV and CpG followed by e1eeuofusion with a HMMA2.5 fusion partner cell line to produce fully human MAbs (fhMAB) SpecifIC for three select agents: Junin virus, Nipah virus, and Rift. VaHey fever virus. The choice of targets is based on data indicating a potential therapeutic role for passive immunotherapy and the avaHability well-characterized clinical materials. A limited evaluation of MFP-2 has been oonducted in the context of ding an INO with the FDA. Furthennore, a commercial relationship has been established with the goal of producing GMP grade fhMAbs for treatment of non-Hodgkin lymphomas. These factors will enable transition of fhMAbs with antiviral activity from animal models to clinical use. Specific aims include: 1. Establish serologic assays for screening of convalescent donor sera and human hybridoma supernatants; 2. Characterize donor sera and PBl, and generate human hybridoma lines; and 3. Test neutraliZing fhMAbs for protective activity in animal models.