Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Front Immunol. 2023 Mar 16;14:1143870. doi: 10.3389/fimmu.2023.1143870. eCollection 2023.
Herpes 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.
We 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.
In 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.
This 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.
单纯疱疹病毒（HSV）引起广泛的人类感染。为了疫苗开发，了解保护相关性至关重要。因此，我们研究了（I）人类是否原则上能够产生针对 HSV 的细胞间传播抑制抗体，以及（II）这种能力是否与降低 HSV-1 再激活风险相关。
我们建立了一种高通量 HSV-1-ΔgE-GFP 报告病毒基于的测定法，并评估了 2496 个人类血浆样本中 HSV-1 糖蛋白 E（gE）非依赖性细胞间传播抑制抗体。随后，我们对献血者进行了回顾性调查，以分析血浆中存在细胞间传播抑制抗体与 HSV 再激活频率之间的相关性。
在总共 2496 名献血者中，有 128 名（5.1%）的血浆中显示出高水平的 HSV-1 gE 非依赖性细胞间传播抑制抗体。在 147 份 HSV-1 血清阴性的血浆中，没有一份表现出部分或完全的细胞间传播抑制，证明了我们测定法的特异性。具有细胞间传播抑制抗体的个体与没有足够水平的此类抗体的受试者相比，HSV 再激活的频率显著降低。
这项研究有两个重要发现：（I）在自然 HSV 感染后，一些人类会产生细胞间传播抑制抗体，以及（II）这种抗体与预防复发性 HSV-1 相关。此外，这些精英中和抗体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。
