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Volume 15
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10.3390/v15081686
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Article

The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice

by
Isabella Skandorff
1,2,
Jasmin Gille
3,
Emeline Ragonnaud
2,4,
Anne-Marie Andersson
2,
Silke Schrödel
5,
Christian Thirion
5,
Ralf Wagner
3 and
Peter Johannes Holst
2,4,*
1
Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
2
InProTher, COBIS, Ole Maaloesvej 3, 2200 Copenhagen, Denmark
3
Institute of Medical Microbiology and Hygiene, Molecular Microbiology, University of Regensburg Germany, 93053 Regensburg, Germany
4
Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
5
Sirion Biotech GmbH, Am Haag 6, 82166 Graefelfing, Germany
*
Author to whom correspondence should be addressed.
Viruses 2023, 15(8), 1686; https://doi.org/10.3390/v15081686
Submission received: 6 June 2023 / Revised: 30 July 2023 / Accepted: 31 July 2023 / Published: 3 August 2023
(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)
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Abstract

Human endogenous retrovirus type W (HERV-W) is expressed in various cancers. We previously developed an adenovirus-vectored cancer vaccine targeting HERV-W by encoding an assembled HERV-W group-specific antigen sequence and the HERV-W envelope sequence Syncytin-1. Syncytin-1 is constitutively fusogenic and forms large multinucleated cell fusions when overexpressed. Consequently, immunising humans with a vaccine encoding Syncytin-1 can lead to the formation of extensive syncytia, which is undesirable and poses a potential safety issue. Here, we show experiments in cell lines that restoring an evolutionary lost cleavage site of the fusion inhibitory R-peptide of Syncytin-1 inhibit cell fusion. Interestingly, this modification of the HERV-W vaccine’s fusogenicity increased the expression of the vaccine antigens in vitro. It also enhanced Syncytin-1-specific antibody responses and CD8+-mediated T-cell responses compared to the wildtype vaccine in vaccinated mice, with a notable enhancement in responses to subdominant T-cell epitopes but equal responses to dominant epitopes and similar rates of survival following a tumour challenge. The impairment of cell–cell fusion and the enhanced immunogenicity profile of this HERV-W vaccine strengthens the prospects of obtaining a meaningful immune response against HERV-W in patients with HERV-W-overexpressing cancers.
Keywords: adenoviral vector; cell fusion; human endogenous retrovirus type W (HERV-W); R-peptide; Syncytin-1 adenoviral vector; cell fusion; human endogenous retrovirus type W (HERV-W); R-peptide; Syncytin-1

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MDPI and ACS Style

Skandorff, I.; Gille, J.; Ragonnaud, E.; Andersson, A.-M.; Schrödel, S.; Thirion, C.; Wagner, R.; Holst, P.J. The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice. Viruses 2023, 15, 1686. https://doi.org/10.3390/v15081686

AMA Style

Skandorff I, Gille J, Ragonnaud E, Andersson A-M, Schrödel S, Thirion C, Wagner R, Holst PJ. The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice. Viruses. 2023; 15(8):1686. https://doi.org/10.3390/v15081686

Chicago/Turabian Style

Skandorff, Isabella, Jasmin Gille, Emeline Ragonnaud, Anne-Marie Andersson, Silke Schrödel, Christian Thirion, Ralf Wagner, and Peter Johannes Holst. 2023. "The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice" Viruses 15, no. 8: 1686. https://doi.org/10.3390/v15081686

APA Style

Skandorff, I., Gille, J., Ragonnaud, E., Andersson, A.-M., Schrödel, S., Thirion, C., Wagner, R., & Holst, P. J. (2023). The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice. Viruses, 15(8), 1686. https://doi.org/10.3390/v15081686

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