Belgian researchers uncover how dendritic cells respond to lipid nanoparticles in vaccines

Belgian scientists have uncovered new details about how the immune system responds to vaccines. Dendritic cells, which are key immune messengers that help kick-start the body's defenses, show specific responses to lipid nanoparticles. These findings, published in Cell Reports, could lead to safer and more effective vaccines. 

Dendritic cells and lipid nanoparticles 

Dendritic cells are among the first to detect viruses, bacteria, or other immune challenges. These cells help coordinate the immune system's response by alerting T cells, the immune system's soldiers trained to eliminate threats. But dendritic cells don't always respond in the same way. Some keep the immune system calm and balanced (homeostatic), while others drive a full immune attack (immunogenic). 

Until now, little was known about what determines these different responses, especially when dendritic cells encounter vaccines. 

The team of Prof. Sophie Janssens (VIB-UGent Center for Inflammation), and colleagues at the University of Ghent, the VIB Single Cell Core, and the University of Brussels, investigated how dendritic cells react to lipid nanoparticles (LNPs), the technology used in mRNA vaccines. LNPs are tiny spheres that deliver genetic instructions to immune cells, prompting them to produce virus-fighting proteins. 

Calm or activated? 

Using cutting-edge methods like CITE-sequencing and flow cytometry, the researchers discovered that LNPs can influence dendritic cells to adopt either a calm, homeostatic role or an activated, immunogenic one. 

We found that empty LNPs don't strongly activate the immune system. That's good news, because it means they can deliver vaccine components without triggering unintended inflammation. But more importantly, by choosing what we load into them, we can steer the immune response in specific ways." 

Dr. Sofie Rennen (VIB-UGent), first author of the study

For example, LNPs carrying antigens encoded as mRNA molecules prompted dendritic cells to take on an immunogenic role: activating T cells and driving protection. In contrast, empty LNPs or LNPs carrying peptides supported a more homeostatic profile, potentially useful for promoting immune tolerance. 

Dr. Victor Bosteels (VIB-UGent), co-first author, adds, "Our work might lay the groundwork for 'calming' vaccines for autoimmune diseases by encouraging a healthy immune system instead of inflammation." 

"Overall," says Prof. Janssens (VIB-UGent), "mapping how dendritic cells respond to different vaccine elements allows us to target the immune system more precisely and safely, which can lead to the next generation of vaccines."