Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD‐2 epitope is a highly conserved linear neutralizing epitope of gB and a critical target for antibodies; however, only 50% of sero‐positive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD‐2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of sero‐positive individuals improved pre‐existing gB‐specific IgA and IgG levels and induced de novo gB‐specific IgA and IgG responses in sero‐negative recipients. Pre‐existing AD‐2 IgG and IgA responses were boosted with vaccination, but de novo AD‐2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD‐2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD‐2 was observed within human breastmilk samples. All antibodies binding AD‐2 contained kappa light chains, whereas balanced kappa/lambda light chain usage was found for those binding to gB. V region‐matched AD‐2‐specific recombinant IgG and IgA bound both to gB and to AD‐2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD‐2 are a significant component of human milk, which may function to protect neonates from HCMV.

中文翻译：

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IgA 与糖蛋白 B 的 AD-2 表位结合并中和人巨细胞病毒

人巨细胞病毒 (HCMV) 是一种普遍存在的病原体，在原发感染期间对免疫抑制个体和孕妇具有潜在致病性。HCMV 包膜糖蛋白 B (gB) 促进病毒进入所有细胞类型并诱导有效的免疫反应。AD-2 表位是 gB 的高度保守的线性中和表位，是抗体的关键靶标；然而，只有 50% 的血清阳性个体会针对该位点产生 IgG 抗体，并且 IgA 反应尚未得到充分研究。本研究旨在比较自然暴露个体和接受重组 gB/MF59 佐剂疫苗的个体中针对 gB 和 AD-2 表位的 IgG 和 IgA 反应。因此，血清阳性个体的疫苗接种改善了预先存在的 gB 特异性 IgA 和 IgG 水平，并在血清阴性接受者中诱导了新的 gB 特异性 IgA 和 IgG 反应。疫苗接种增强了预先存在的 AD-2 IgG 和 IgA 反应，但未检测到新的 AD-2 反应。与较弱和可变的 IgA 反应相比，自然暴露的个体对 gB 和 AD-2 具有显着的 IgG 反应，尽管在人类母乳样本中观察到对 AD-2 的显着 IgA 结合反应。所有结合 AD-2 的抗体都含有 kappa 轻链，而在那些结合 gB 的抗体中发现了平衡的 kappa/lambda 轻链使用。V 区匹配的 AD-2 特异性重组 IgG 和 IgA 结合 gB 和 AD-2，并在体外中和 HCMV 感染。总的来说，这些结果表明，虽然人类 IgG 反应占主导地位，