Non-cytolytic re-engineering of a viral vaccine vector enables durable effector-memory T cell immunity by reinforcing type I IFN induction

Molecular Therapy — Nucleic Acids 2026 Open access

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Authors: Matías Ciancaglini, Robin Avanthay, Anna‐Friederike Marx, Tiago Abreu-Mota, Davide Finozzi, Jonas Fixemer, Florian M. Geier, Dominik Bürri, Ingrid Wagner, Ilena Vincenti, Mario Kreuzfeldt, Doron Merkler
+2 more Gert Zimmer, Daniel D. Pinschewer
DOI: 10.1016/j.omtn.2026.102852
Cited by: 1
References: 110

Abstract

challenge. Improved CD8 T cell responses of non-cytolytic rVSVMq were driven by a reinforced type I interferon (IFN-I) response and its direct sensing by vaccination-induced CD8 T cells. Many vector cargo-specific CD8 T cells in the splenic marginal zone of rVSVMq- or rLCMV-vaccinated mice were in contact with vector cargo-expressing cells that co-expressed IFN-I. In contrast, rVSV-vectored cargo-expressing contacts of specific CD8 T cells were largely IFN I-negative. Thereby, vaccination with non-cytolytic viral vectors offered an opportunity for CD8 T cells to integrate peptide-MHC (major histocompatibility complex) and IFN-I signals during priming. These mechanistic insights should help to refine vaccines aimed at eliciting durable and protective effector-memory CD8 T cell immunity.

Fields of Study & Subjects

Immunotherapy and Immune Responses interferon and immune responses Virus-based gene therapy research

Publication details

Journal / source
Molecular Therapy — Nucleic Acids
Publisher
Elsevier BV
Volume
37
Issue
1
Pages
102852–102852
Publication date
3 February 2026
Language
EN