Chimeric SARS-CoV-2 vaccine vectors stably incorporating the functional glycoprotein of VSV.

Authors

Enja Tatjana Kipfer, Jacob Schön, Mohamed Chami, Stefan Finke, Martin Beer, Donata Hoffmann, Fabian Otte, David Hauser

Published in

iScience. Volume 29. Issue 10. Pages 117521. Oct 16, 2026. Epub Sep 16, 2026.

Abstract

Respiratory viruses, such as SARS-CoV-2, remain a global medical challenge, highlighting the need for adaptable vaccine platforms that elicit broad immunity while allowing flexible antigen design. Building on our established envelope-deleted (ΔE) SARS-CoV-2 vaccine candidate, we engineered chimeric variants that stably express the glycoprotein of vesicular stomatitis virus (VSV-G) as a model antigen, with or without co-expression of the native SARS-CoV-2 spike protein. Both constructs were genetically stable and displayed functional VSV-G, as shown by expanded, ACE2-independent tropism. Cryo-electron microscopy confirmed the presence of heterologous glycoproteins on virions. In vivo, both chimeric viruses exhibited an excellent safety profile and induced antigen-specific humoral responses against the encoded glycoproteins in Syrian hamsters and K18-hACE2 mice. Together, these findings demonstrate stable genetic incorporation and display of a functional heterologous glycoprotein into a SARS-CoV-2 virion, supporting use of the ΔE SARS-CoV-2 backbone as a potential platform for viral vector engineering and heterologous antigen delivery.

PMID:
42781491
Bibliographic data and abstract were imported from PubMed on 25 Sep 2026.

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