Prabhu Nayana, Prabakaran Mookkan, Hongliang Qian, He Fang, Ho Hui-Ting, Qiang Jia, Goutama Michael, Lim Angeline Pei-Chiew, Hanson Brendon J, Kwang Jimmy
Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore.
Antivir Ther. 2009;14(7):911-21. doi: 10.3851/IMP1413.
Recent outbreaks of highly pathogenic H5N1 viruses in humans indicate that no endogenous protection exists in the general population. Vaccination programmes against this new pathogen require synthesis of endogenous antibodies and cannot provide any immediate protection in the event of a pandemic. Passive immunization with humanized neutralizing monoclonal antibodies can prove to be promising in preventing a catastrophic pandemic.
A murine monoclonal antibody (mAb) 3B1 of immunoglobulin M isotype was switched to a chimeric immunoglobulin G1. BALB/c mice were used to study the protective efficacy of the chimeric mAbs against a lethal H5N1 virus challenge with strains from clades 1 and 2.1. Kinetics of the viral load were determined during the course of the treatment.
The chimeric mAb, in passive administration, was able to protect 100% of the mice when challenged with H5N1 strains from clades 1 or 2.1. Prophylaxis at 1 day prior to challenge and treatment at 1 day after challenge with this mAb resulted in the clearance of the virus from the lungs of the infected mice within 6 days post-viral challenge.
Passive immunotherapy using chimeric mAb 3B1 can be an effective tool in both the prophylaxis and treatment of highly pathogenic H5N1 infection, providing the immediate immunity needed to contain a future influenza pandemic.
近期高致病性H5N1病毒在人类中的爆发表明，普通人群中不存在内源性保护。针对这种新病原体的疫苗接种计划需要合成内源性抗体，并且在大流行发生时无法提供任何即时保护。用人源化中和单克隆抗体进行被动免疫在预防灾难性大流行方面可能很有前景。
将免疫球蛋白M同种型的鼠单克隆抗体（mAb）3B1转换为嵌合免疫球蛋白G1。使用BALB/c小鼠研究嵌合单克隆抗体对来自1和2.1分支的致死性H5N1病毒攻击的保护效果。在治疗过程中测定病毒载量的动力学。
在被动给药时，嵌合单克隆抗体在用来自1或2.1分支的H5N1毒株攻击时能够保护100%的小鼠。在攻击前1天进行预防和在攻击后1天用该单克隆抗体进行治疗导致在病毒攻击后6天内从感染小鼠的肺部清除病毒。
使用嵌合单克隆抗体3B1进行被动免疫治疗可以成为预防和治疗高致病性H5N1感染的有效工具，提供遏制未来流感大流行所需的即时免疫力。
