Rapid protection against viral infections by chemokine-accelerated post-exposure vaccination.

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 -galactosylceramide to induce signal 0-chemokines. Exploiting this vaccination model, we studied detailed T cell kinetics and T cell profiling in different 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.

Copyright © 2024 Heine, Lemmermann, Flores, Becker-Gotot, Garbi, Brossart and Kurts.

PMID: 38348028