Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.

中文翻译：

---

母体 Fc 介导的非中和抗体反应与预防先天性人类巨细胞病毒感染相关

人类巨细胞病毒 (HCMV) 是最常见的先天性感染，也是全世界死产、神经发育障碍和小儿听力损失的主要原因。由于对防止 HCMV 在子宫内传播的免疫反应了解有限，阻碍了预防先天性 HCMV 的母体疫苗或治疗方法的开发。为了确定保护性抗体反应，我们测量了配对母体和脐带血血清中的 HCMV 特异性 IgG 结合和抗病毒功能，这些血清来自通过大量鉴定的 HCMV 血清阳性传播 (n = 41) 和非传播 (n = 40)母婴二元组。 ，总部位于美国的公共脐带血库。我们发现，高亲和力 IgG 与 HCMV 结合和抗体依赖性细胞吞噬作用 (ADCP) 与先天性 HCMV 感染风险降低相关。我们还确定，在非传递二元体中，FcγRI 和 FcγRII 的 HCMV 特异性 IgG 激活增强，并且 ADCP 反应的增加是通过人单核细胞上表达的 FcγRI 和 FcγRIIA 介导的。这些研究结果表明，FcγRI/FcγRIIA 和 Fc 效应器功能（包括 ADCP）的结合可以预防先天性 HCMV 感染。总而言之，这些数据可以指导未来针对先天性 HCMV 传播的免疫相关性的前瞻性研究，并为 HCMV 疫苗和免疫治疗的开发提供信息。