BackgroundHerpes simplex viruses (HSV) cause ubiquitous human infections. For vaccine development, knowledge concerning correlates of protection is essential. Therefore, we investigated (I) if humans are in principle capable producing cell-to-cell spread inhibiting antibodies against HSV and (II) whether this capacity is associated with a reduced HSV-1 reactivation risk.MethodsWe established a high-throughput HSV-1-ΔgE-GFP reporter virus-based assay and evaluated 2,496 human plasma samples for HSV-1 glycoprotein E (gE) independent cell-to-cell spread inhibiting antibodies. Subsequently, we conducted a retrospective survey among the blood donors to analyze the correlation between the presence of cell-to-cell spread inhibiting antibodies in plasma and the frequency of HSV reactivations.ResultsIn total, 128 of the 2,496 blood donors (5.1%) exhibited high levels of HSV-1 gE independent cell-to-cell spread inhibiting antibodies in the plasma. None of the 147 HSV-1 seronegative plasmas exhibited partial or complete cell-to-cell spread inhibition, demonstrating the specificity of our assay. Individuals with cell-to-cell spread inhibiting antibodies showed a significantly lower frequency of HSV reactivations compared to subjects without sufficient levels of such antibodies.ConclusionThis study contains two important findings: (I) upon natural HSV infection, some humans produce cell-to-cell spread inhibiting antibodies and (II) such antibodies correlate with protection against recurrent HSV-1. Moreover, these elite neutralizers may provide promising material for immunoglobulin therapy and information for the design of a protective vaccine against HSV-1.

中文翻译：

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细胞间传播抑制抗体与 1 型单纯疱疹病毒再激活的保护作用相关：一项回顾性研究

背景单纯疱疹病毒 (HSV) 引起普遍存在的人类感染。对于疫苗开发，有关保护相关性的知识是必不可少的。因此，我们调查了 (I) 人类原则上是否能够产生针对 HSV 的细胞间传播抑制抗体，以及 (II) 这种能力是否与降低的 HSV-1 再激活风险相关。方法我们建立了高通量 HSV-基于 1-ΔgE-GFP 报告基因病毒的测定，并评估了 2,496 份人类血浆样本的 HSV-1 糖蛋白 E (gE) 独立细胞间传播抑制抗体。随后，我们对献血者进行了一项回顾性调查，以分析血浆中细胞间传播抑制抗体的存在与 HSV 再激活频率之间的相关性。结果总共有 2,496 名献血者中的 128 名 (5. 1%) 在血浆中表现出高水平的 HSV-1 gE 独立细胞间传播抑制抗体。147 种 HSV-1 血清阴性血浆中没有一种表现出部分或完全的细胞间扩散抑制，证明了我们检测的特异性。与没有足够水平此类抗体的受试者相比，具有细胞间传播抑制抗体的个体显示出显着较低的 HSV 再激活频率。结论本研究包含两个重要发现：(I) 在自然 HSV 感染后，一些人产生细胞到-细胞扩散抑制抗体和 (II) 此类抗体与针对复发性 HSV-1 的保护相关。此外，这些精英中和剂可能为免疫球蛋白治疗提供有前途的材料，并为设计针对 HSV-1 的保护性疫苗提供信息。