Passive immune protection by herpes simplex virus-specific monoclonal antibodies and monoclonal antibody-resistant mutants altered in pathogenicity.
Passive immune protection by herpes simplex virus-specific monoclonal antibodies and monoclonal antibody-resistant mutants altered in pathogenicity.
复制标题
单纯疱疹病毒特异性单克隆抗体和致病性改变的单克隆抗体抗性突变体的被动免疫保护。
DOI：
10.1128/jvi.56.3.930-937.1985
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发表时间：
1985
影响因子：
5.4
通讯作者：
Glorioso,JC
中科院分区：
文献类型：
--
作者：
Kumel,G;Kaerner,HC;Levine,M;Schroder,CH;Glorioso,JC
比较了对单纯疱疹病毒1型科斯-321株糖蛋白gC、gB和gD的13种不同遗传定义表位具有特异性的病毒中和单克隆抗体对经颅内激发的DBA-2小鼠提供被动免疫的能力。保护是高度特异性的，因为单个单克隆抗体未能保护免受单克隆抗体抗性（MAR）突变体的感染，这些突变体在注射抗体识别的单个表位中发生改变。被动免疫的剂量反应动力学决定了每种抗体的体外中和滴度。未观察到免疫保护与抗体同种型或补体依赖性体外中和滴度之间的相关性。这表明病毒中和不是保护机制。一般而言，与gC的表位反应的抗体在最低抗体剂量下具有保护性，gB特异性抗体在提供免疫方面效率较低，而针对gD的抗体效率最低。在gC中具有单个表位变化和在gB中具有多个表位变化的mar突变体显示出高度降低的致病性，需要高达5 × 10（6）PFU才能杀死50%的感染动物。这些发现表明抗原变异影响病毒在中枢神经系统中的生长和传播。因此，影响抗原结构的突变也可以改变病毒的致病性。然而，这些表位的改变不会明显减少对感染的抗性的发展。用这些突变体感染小鼠或在攻击前用UV灭活的小鼠感染细胞接种小鼠，使动物对野生型单纯疱疹病毒1型的感染具有抗性。
Virus-neutralizing monoclonal antibodies specific for 13 different genetically defined epitopes of glycoproteins gC, gB, and gD of herpes simplex virus type 1, strain KOS-321, were compared for their ability to provide passive immunity to DBA-2 mice challenged intracranially. Protection was highly specific, since individual monoclonal antibodies failed to protect against infection with monoclonal antibody-resistant (mar) mutants altered in the single epitope recognized by the injected antibody. The dose-response kinetics of passive immunity paralleled the in vitro neutralization titers for each antibody. No correlation was observed between immune protection and antibody isotype or complement-dependent in vitro neutralization titers. This suggests that virus neutralization was not the protective mechanism. In general, antibodies reactive with epitopes of gC were protective at the lowest antibody doses, antibodies specific for gB were less efficient in providing immunity, and antibodies against gD were the least effective. mar mutants with single epitope changes in gC and multiple epitope changes in gB showed highly reduced pathogenicity, requiring up to 5 X 10(6) PFU to kill 50% of infected animals. These findings indicated that antigenic variation affects virus growth and spread in the central nervous system. Thus, mutations which affect antigenic structure also can alter virus pathogenicity. The alteration of these epitopes does not, however, appreciably reduce the development of resistance to infection. Infection of mice with these mutants or inoculation of mice with UV-inactivated, mutant-infected cells before challenge rendered the animals resistant to infection with wild-type herpes simplex virus type 1.