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【文摘发布】H5N1禽流感人单克隆抗体的预防与治
Author: Simmons CP, Bernasconi NL, Suguitan AL, Mills K, Ward JM, Chau NV, Hien TT, Sallusto F, Ha do Q, Farrar J, de Jong MD, Lanzavecchia A, Subbarao K.
Source：PLoS Med. 2007 May;4(5):e178.
Abstract: BACKGROUND: New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection. METHODS AND FINDINGS: Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1). CONCLUSIONS: These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.
PMID: 17535101 [PubMed - in process] 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Title: Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.
标题：人类H5N1型禽流感单克隆抗体的预防与治疗效果
Author: Simmons CP, Bernasconi NL, Suguitan AL, Mills K, Ward JM, Chau NV, Hien TT, Sallusto F, Ha do Q, Farrar J, de Jong MD, Lanzavecchia A, Subbarao K.
Source：PLoS Med. 2007 May;4(5):e178.
Abstract: BACKGROUND: New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection.
摘要：背景：制定人类感染高致病性禽流感H5N1型病毒的新的预防与治疗方法已成为当务之急。我们研制出了人类抗H5N1型中和性单克隆抗体（mAbs）并在小鼠感染模型中验证了其预防与治疗效果。
METHODS AND FINDINGS: Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1).
方法与结果：我们从HPAI H5N1型病毒感染后恢复的越南成年患者提取出记忆性B细胞，并使用EB病毒使其永生化。应用病毒中和试验筛选B细胞系的上清液，克隆分泌中和性抗体的B细胞系并纯化分泌的单克隆抗体。应用中和试验体外检测这些抗体对不同H5N1病毒株的交叉反应，并在小鼠身上检测体内的预防和治疗效果。结果发现，单克隆抗体FLA3.14和FLD20.19可在体外中和一类和二类H5N1病毒，而FLA5.10和FLD21.140仅能中和一类病毒。FLA3.14和FLA5.10以剂量依赖性方式对A/Vietnam/1203/04 H5N1感染小鼠提供保护使其免于死亡。单克隆抗体可显著降低肺部病毒的滴定量，减少相应的肺部炎症，并限制病毒向肺外部扩散。治疗量的FLA3.14、FLA5.10、FLD20.19和 FLD21.140对A/Vietnam/1203/04 H5N1感染带来的致死性提供强有力的保护，这种保护至少长达72小时。同样，单克隆抗体FLA3.14、FLD21.140和FLD20.19可以治疗二类病毒A/Indonesia/5/2005的体内感染，而FLA5.10没有这种治疗作用
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作者:admin@医学,生命科学 2011-03-26 17:11
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