Cell-to-cell spread inhibiting antibodies constitute a correlate of protection against herpes simplex virus type 1 reactivations: A retrospective study.

Autor:	Alt M; 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., Wolf S; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., van de Sand L; Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Dittrich R; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Tertel T; Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Brochhagen L; Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Dirks M; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Aufderhorst UW; 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., Thümmler L; Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Otte M; Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Rainer K; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and University Hospital Ulm, Ulm, Germany.; Institute for Transfusion Medicine, University of Ulm, Ulm, Germany., Dittmer U; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Giebel B; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and University Hospital Ulm, Ulm, Germany., Trilling M; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Silke Heilingloh C; Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Lotfi R; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and University Hospital Ulm, Ulm, Germany.; Institute for Transfusion Medicine, University of Ulm, Ulm, Germany., Roggendorf M; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Witzke O; Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Krawczyk A; 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.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Mar 16; Vol. 14, pp. 1143870. Date of Electronic Publication: 2023 Mar 16 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1143870
Abstrakt:	Background: 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. Methods: 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. Results: 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. Conclusion: 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Alt, Wolf, van de Sand, Dittrich, Tertel, Brochhagen, Dirks, Aufderhorst, Thümmler, Otte, Rainer, Dittmer, Giebel, Trilling, Silke Heilingloh, Lotfi, Roggendorf, Witzke and Krawczyk.)
Databáze:	MEDLINE
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