Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Heine, A; Lemmermann, NAW; Flores, C; Becker-Gotot, J; Garbi, N; Brossart, P; Kurts, C.
Rapid protection against viral infections by chemokine-accelerated post-exposure vaccination.
Front Immunol. 2024; 15: 1338499
Doi: 10.3389/fimmu.2024.1338499
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- Führende Autor*innen der Med Uni Graz
- Heine Annkristin
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- Abstract:
- INTRODUCTION: Prophylactic vaccines generate strong and durable immunity to avoid future infections, whereas post-exposure vaccinations are intended to establish rapid protection against already ongoing infections. Antiviral cytotoxic CD8+ T cells (CTL) are activated by dendritic cells (DCs), which themselves must be activated by adjuvants to express costimulatory molecules and so-called signal 0-chemokines that attract naive CTL to the DCs. HYPOTHESIS: Here we asked whether a vaccination protocol that combines two adjuvants, a toll-like receptor ligand (TLR) and a natural killer T cell activator, to induce two signal 0 chemokines, synergistically accelerates CTL activation. METHODS: We used a well-characterized vaccination model based on the model antigen ovalbumin, the TLR9 ligand CpG and the NKT cell ligand α-galactosylceramide to induce signal 0-chemokines. Exploiting this vaccination model, we studied detailed T cell kinetics and T cell profiling in different in vivo mouse models of viral infection. RESULTS: We found that CTL induced by both adjuvants obtained a head-start that allowed them to functionally differentiate further and generate higher numbers of protective CTL 1-2 days earlier. Such signal 0-optimized post-exposure vaccination hastened clearance of experimental adenovirus and cytomegalovirus infections. CONCLUSION: Our findings show that signal 0 chemokine-inducing adjuvant combinations gain time in the race against rapidly replicating microbes, which may be especially useful in post-exposure vaccination settings during viral epi/pandemics.
- Find related publications in this database (using NLM MeSH Indexing)
- Mice - administration & dosage
- Animals - administration & dosage
- CD8-Positive T-Lymphocytes - administration & dosage
- Ligands - administration & dosage
- Chemokines - administration & dosage
- Adjuvants, Immunologic - pharmacology
- Vaccination - methods
- Virus Diseases - administration & dosage
- Find related publications in this database (Keywords)
- chemokines
- CTL induction
- post-exposure vaccination
- murine cytomegalovirus
- viral infection
- NKT cells
- TLR ligand
- adenovirus