Rybniker, Jan | Theobald, Sebastian - B 08

Recent scientific advances in vaccine research have demonstrated that innate immune cells can develop a memory-like phenotype termed trained innate immunity (TII), which leads to enhanced responsiveness upon secondary challenge. While traditionally associated with live vaccines such as BCG, our recent work has shown that mRNA-based vaccines targeting SARS-CoV-2 also induce TII through durable epigenetic and transcriptional reprogramming. These responses are linked to increased cytokine production and improved innate-adaptive immune crosstalk in stimulated innate immune cells. However, the molecular mechanisms and functional consequences of vaccine-induced TII remain incompletely understood. 

In this project, we will dissect the capacity of protein subunit- and mRNA-based vaccines to induce TII in vivo using murine models of SARS-CoV-2 and RSV vaccination. We will integrate transcriptomic and epigenomic profiling as well as functional assays to identify the key molecular determinants and immune cell subsets involved in TII. Furthermore, we will evaluate the potential of TII to mediate cross-protection against unrelated pathogens, aiming to establish proof-of-concept for broad-spectrum immune potentiation through vaccination. These insights will help optimize vaccine design and provide a translational foundation for improved prophylactic strategies, particularly in vulnerable populations with impaired adaptive immunity.