Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice.
Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice.
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DOI：
10.1186/1465-9921-7-126
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发表时间：
2006-10-14
影响因子：
5.8
通讯作者：
Webby RJ
中科院分区：
文献类型：
--
作者：
Hanson BJ;Boon AC;Lim AP;Webb A;Ooi EE;Webby RJ
高致病性H5 N1禽流感病毒是一个重大的公共卫生问题。由于缺乏有效的疫苗和最近的证据表明，抗病毒药物耐药性的一些分离株，替代战略，遏制未来可能的大流行是必要的。中和H5 N1病毒的人源化单克隆抗体（mAb）可用作预防和治疗，以帮助遏制这种大流行。将针对H5血凝素的中和mAb人源化，并在用H5 N1 A/Vietnam/1203/04病毒致死攻击前一天、致死攻击后一天和致死攻击后三天引入C57 BL/6小鼠（1、5或10 mg/kg体重）。通过观察体重减轻以及存活率来确定疗效。鉴定了两种中和抗原性变异H5 N1病毒的mAb，A/Vietnam/1203/04和A/Hong Kong/213/03，并在不丧失特异性的情况下进行人源化。两种抗体在小鼠中均表现出预防功效，然而，VN 04 -2-huGl表现更好，仅需要lmg/kg体重就能完全保护。当用于治疗感染时，VN 04 -2-huG 1也具有完全保护作用，即使在感染后三天引入也是如此，尽管需要更高剂量的抗体。使用中和人源化mAb的预防和治疗对A/Vietnam/1203/04致死性攻毒有效，为在大流行性流感事件中使用被动抗体治疗作为遏制选择提供了原则证据。
Highly pathogenic avian H5N1 influenza virus is a major public health concern. Given the lack of effective vaccine and recent evidence of antiviral drug resistance in some isolates, alternative strategies for containment of a possible future pandemic are needed. Humanized monoclonal antibodies (mAbs) that neutralize H5N1 virus could be used as prophylaxis and treatment to aid in the containment of such a pandemic. Neutralizing mAbs against H5 hemagglutinin were humanized and introduced into C57BL/6 mice (1, 5, or 10 mg/kg bodyweight) one day prior to-, one day post- and three days post-lethal challenge with H5N1 A/Vietnam/1203/04 virus. Efficacy was determined by observation of weight loss as well as survival. Two mAbs neutralizing for antigenically variant H5N1 viruses, A/Vietnam/1203/04 and A/Hong Kong/213/03 were identified and humanized without loss of specificity. Both antibodies exhibited prophylactic efficacy in mice, however, VN04-2-huG1 performed better requiring only 1 mg/kg bodyweight for complete protection. When used to treat infection VN04-2-huG1 was also completely protective, even when introduced three days post infection, although higher dose of antibody was required. Prophylaxis and treatment using neutralizing humanized mAbs is efficacious against lethal challenge with A/Vietnam/1203/04, providing proof of principle for the use of passive antibody therapy as a containment option in the event of pandemic influenza.
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影响因子：
56.9
作者：
Kuiken, T;Rimmelzwaan, G;Osterhaus, A
通讯作者：
Osterhaus, A
影响因子：
11.8
作者：
Keawcharoen J;Oraveerakul K;Kuiken T;Fouchier RA;Amonsin A;Payungporn S;Noppornpanth S;Wattanodorn S;Theambooniers A;Tantilertcharoen R;Pattanarangsan R;Arya N;Ratanakorn P;Osterhaus DM;Poovorawan Y
通讯作者：
Poovorawan Y
影响因子：
168.9
作者：
Claas, ECJ;Osterhaus, ADME;Webster, RG
通讯作者：
Webster, RG
DOI：
10.1073/pnas.0506416102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Hoffmann, E;Lipatov, AS;Webster, RG
通讯作者：
Webster, RG
DOI：
10.1073/pnas.0511120103
发表时间：
2006-02-21
影响因子：
11.1
作者：
Chen, H;Smith, GJD;Guan, Y
通讯作者：
Guan, Y