Skandorff, Isabella and Gille, Jasmin and Ragonnaud, Emeline and Andersson, Anne-Marie and Schroedel, Silke and Thirion, Christian and Wagner, Ralf and Holst, Peter Johannes (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-BASEL, 15 (8): 1686. ISSN , 1999-4915
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RETROVIRUS HERV-W; ENVELOPE GLYCOPROTEIN; METHYLATION; ACTIVATION; EXPRESSION; PLACENTA; IMMUNITY; adenoviral vector; cell fusion; human endogenous retrovirus type W (HERV-W); R-peptide; Syncytin-1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2024 09:23 |
| Last Modified: | 23 Mar 2024 09:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60396 |
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