Antibody-mediated neutralization of cytomegalovirus: modulation of efficacy induced through the IgG constant region
Antibody-mediated neutralization of cytomegalovirus: modulation of efficacy induced through the IgG constant region
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DOI：
10.1016/s0161-5890(01)00119-5
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发表时间：
2002-03-01
影响因子：
3.6
通讯作者：
Ohlin, M
中科院分区：
文献类型：
--
作者：
Furebring, C;Speckner, A;Ohlin, M
抗体可以中和人巨细胞病毒（CMV）的感染特性。在体内，主要的中和决定簇位于糖蛋白B（gB）上。研究了携带针对这些表位中的两个的不同恒定区（IgG 1、IgG 3和合成变体IgG 3 mA）的重组人抗体募集补体级联以破坏病毒的能力。结果表明，尽管观察到IgG 3和IgG 3 mA的C1 q结合优于IgG 1变体，但针对抗原结构域（AD）-2表位的抗体的所有变体均显示出相似的中和活性。相比之下，携带正常IgG 3恒定区的抗AD-1表位的抗体在不存在补体的情况下中和病毒的效率低于其IgG 1对应物。然而，在补体存在下，其活性恢复至天然存在的IgG 1版本的水平。如果相同的抗体携带IgG 3 mA恒定区，则其在补体存在下中和病毒的效力显著更强。这证明了恒定结构域对于AD-1特异性抗体的生物活性的重要性，当使用基于抗体的治疗剂或当通过疫苗接种诱导抗体时，这是应该考虑的因素。(C)2002爱思唯尔科技有限公司版权所有。
Antibodies can neutralize the infectious properties of human cytomegalovirus (CMV). In vivo, the major neutralization determinants are located on glycoprotein B (gB). Recombinant human antibodies, that carry different constant regions (IgG1, IgG3 and the synthetic variant IgG3mA) against two of these epitopes were investigated for their ability to recruit the complement cascade for destruction of the virus. It was shown that all variants of an antibody against the antigenic domain (AD)-2 epitope displayed a similar neutralization activity despite the fact that improved C1q binding was observed for IgG3 and IgG3mA over the IgG1 variant. In contrast, an antibody against the AD-1 epitope carrying the normal IgG3 constant region, was less efficient than its IgG1 counterpart in neutralizing the virus in the absence of complement. However, it restored its activity in the presence of complement to the level of the naturally occurring IgG1 version. The same antibody was substantially more potent in neutralizing the virus in the presence of complement if it carried the IgG3mA constant region. This demonstrates the importance of the constant domain for the biological activity of AD-1 specific antibodies, a factor that should be taken into account when using antibody-based therapeutics or when inducing antibodies by vaccination. (C) 2002 Elsevier Science Ltd. All rights reserved.