| First Author | Heine A | Year | 2024 |
| Journal | Front Immunol | Volume | 15 |
| Pages | 1338499 | PubMed ID | 38348028 |
| Mgi Jnum | J:350739 | Mgi Id | MGI:7594548 |
| Doi | 10.3389/fimmu.2024.1338499 | Citation | Heine A, et al. (2024) Rapid protection against viral infections by chemokine-accelerated post-exposure vaccination. Front Immunol 15:1338499 |
| abstractText | 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 alpha-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. |
