Human cytomegalovirus (HCMV) is an important pathogen in transplant patients and in congenital infection. Previously, we demonstrated that vaccination with a recombinant viral glycoprotein B (gB)/MF59 adjuvant formulation before solid organ transplant reduced viral load parameters post transplant. Reduced posttransplant viremia was directly correlated with antibody titers against gB consistent with a humoral response against gB being important. Here we show that sera from the vaccinated seronegative patients displayed little evidence of a neutralizing antibody response against cell-free HCMV in vitro. Additionally, sera from seronegative vaccine recipients had minimal effect on the replication of a strain of HCMV engineered to be cell-associated in a viral spread assay. Furthermore, although natural infection can induce antibody-dependent cellular cytotoxicity (ADCC) responses, serological analysis of seronegative vaccinees again presented no evidence of a substantial ADCC-promoting antibody response being generated de novo. Finally, analyses for responses against major antigenic domains of gB following vaccination were variable, and their pattern was distinct compared with natural infection. Taken together, these data argue that the protective effect elicited by the gB vaccine is via a mechanism of action in seronegative vaccinees that cannot be explained by neutralization or the induction of ADCC. More generally, these data, which are derived from a human challenge model that demonstrated that the gB vaccine is protective, highlight the need for more sophisticated analyses of new HCMV vaccines over and above the quantification of an ability to induce potent neutralizing antibody responses in vitro.

人巨细胞病毒 (HCMV) 是移植患者和先天性感染的重要病原体。以前，我们证明在实体器官移植前用重组病毒糖蛋白 B (gB)/MF59 佐剂制剂接种疫苗可降低移植后的病毒载量参数。减少的移植后病毒血症与针对 gB 的抗体滴度直接相关，这与针对 gB 的重要体液反应一致。在这里，我们显示来自接种疫苗的血清反应阴性患者的血清在体外几乎没有显示针对无细胞 HCMV 的中和抗体反应的证据。此外，来自血清反应阴性疫苗接受者的血清对在病毒传播测定中被设计为与细胞相关的 HCMV 毒株的复制影响极小。此外，尽管自然感染可诱导抗体依赖性细胞毒性 (ADCC) 反应，但对血清阴性疫苗接种者的血清学分析再次表明，没有证据表明从头产生了大量促进 ADCC 的抗体反应。最后，对接种疫苗后针对 gB 主要抗原结构域的反应进行的分析是可变的，并且与自然感染相比，它们的模式是截然不同的。综上所述，这些数据表明，gB 疫苗引起的保护作用是通过血清反应阴性疫苗接种者的一种作用机制实现的，这种作用机制无法用中和或 ADCC 的诱导来解释。更一般地说，这些数据源自证明 gB 疫苗具有保护作用的人类攻击模型，