Antibodies Targeting KSHV gH/gL Reveal Distinct Neutralization Mechanisms

Fricke T, Großkopf AK, Enßer A, Backovic M, Hahn AS (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Viruses MDPI

Book Volume: 14

Article Number: 541

Journal Issue: 3

DOI: 10.3390/v14030541

Abstract

Kaposi’s sarcoma herpesvirus (KSHV) is associated with a significant disease burden, in particular in Sub-Sahara Africa. A KSHV vaccine would be highly desirable, but the mechanisms underlying neutralizing antibody responses against KSHV remain largely unexplored. The complex made of glycoproteins H and L (gH/gL) activates gB for the fusion of viral and cellular membranes in all herpesviruses. KSHV gH/gL also interacts with cellular Eph family receptors. To identify optimal antigens for vaccination and to elucidate neutralization mechanisms, we primed mice with recombinantly expressed, soluble gH/gL (gHecto/gL) that was either wildtype (WT), lacking defined glycosylation sites or bearing modified glycosylation, followed by boosts with WT gHecto/gL. We also immunized with a gL-gHecto fusion protein or a gHecto-ferritin/gL nanoparticle. Immune sera neutralized KSHV and inhibited EphA2 receptor binding. None of the regimens was superior to immunization with WT gHecto/gL with regard to neutralizing activity and EphA2 blocking activity, the gL-gHecto fusion protein was equally effective, and the ferritin construct was inferior. gH/gL-targeting sera inhibited gB-mediated membrane fusion and inhibited infection also independently from receptor binding and gL, as demonstrated by neutralization of a novel KSHV mutant that does not or only marginally incorporate gL into the gH/gL complex and infects through an Eph-independent route.

Authors with CRIS profile

Armin Enßer Medizinische Fakultät

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

A081: Host cell receptor and neuropathogenicity of mammalian 1 orthobornavirus Jan. 1, 2020 - Dec. 15, 2022

Involved external institutions

Deutsches Primatenzentrum (DPZ), Leibniz-Institut für Primatenforschung DE Germany (DE) National Center for Scientific Research / Centre national de la recherche scientifique (CNRS) FR France (FR)

How to cite

APA:

Fricke, T., Großkopf, A.K., Enßer, A., Backovic, M., & Hahn, A.S. (2022). Antibodies Targeting KSHV gH/gL Reveal Distinct Neutralization Mechanisms. Viruses, 14(3). https://doi.org/10.3390/v14030541

MLA:

Fricke, Thomas, et al. "Antibodies Targeting KSHV gH/gL Reveal Distinct Neutralization Mechanisms." Viruses 14.3 (2022).

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