Kinetics of protective antibodies are determined by the viral surface antigen
Kinetics of protective antibodies are determined by the viral surface antigen
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DOI：
10.1172/jci200422374
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发表时间：
2004-10-01
影响因子：
15.9
通讯作者：
Zinkernagel, RM
中科院分区：
文献类型：
--
作者：
Pinschewer, DD;Perez, M;Zinkernagel, RM
延迟和弱的病毒中和抗体（nAb）反应是一个标志，不仅与建立持续感染，而且与不成功的疫苗开发。使用反向遗传学方法，我们评估了2种广泛研究的病毒感染模型中可能的潜在机制。交换淋巴细胞性脉络丛脑膜炎病毒（LCMV，天然持久性、非细胞溶解性、无效nAb诱导剂）和水泡性口炎病毒（VSV，非持久性、细胞溶解性、有效nAb诱导剂）的糖蛋白（GP），将nAb的唯一靶标从任一病毒转移到另一病毒。我们分析了感染小鼠中对2种重组病毒和亲本病毒的nAb应答，发现nAb动力学仅由病毒表面GP决定，而不是由病毒骨架决定。此外，缓慢和不良的nAb触发LCMV病毒粒子是一个强大的免疫原性矩阵更具抗原性的VSV-GP。这些发现表明，病毒GP决定nAb动力学在很大程度上独立于特定的病毒感染背景。他们进一步表明，病毒GP的结构特征或病毒GP对宿主幼稚B细胞库的共进化适应，或两者，可能严重限制nAb动力学和疫苗效力的改善。
Delayed and weak virus neutralizing antibody (nAb) responses represent a hallmark correlating not only with the establishment of persistent infection but also with unsuccessful vaccine development. Using a reverse genetic approach, we evaluated possible underlying mechanisms in 2 widely studied viral infection models. Swapping the glycoproteins (GPs) of lymphocytic choriomeningitis virus (LCMV, naturally persisting, noncytolytic, inefficient nAb inducer) and vesicular stomatitis virus (VSV, nonpersisting, cytolytic, potent nAb inducer) transferred the only target of nAb's from either virus to the other. We analyzed the nAb response to each of the 2 recombinant and parent viruses in infected mice and found that nAb kinetics were solely determined by the viral surface GP and not by the virus backbone. Moreover, the slowly and poorly nAb-triggering LCMV virion was a potent immunogenic matrix for the more antigenic VSV-GP. These findings indicate that the viral GP determines nAb kinetics largely independently of the specific viral infection context. They further suggest that structural features of viral GPs or coevolutionary adaptation of the virus's GP to the host's naive B cell repertoire, or both, may critically limit nAb kinetics and improvement of vaccine efficacy.