Understanding Mechanisms of mRNA Vaccination

Few medical innovations have saved as many lives as vaccines against infectious diseases. During the SARS-CoV-2 pandemic, the first mRNA vaccines were approved for humans.

The development of vaccines based on mRNA encoding for antigens has emerged as a new era and the potential impact is immense both in terms of immunogenicity and cost reduction.

However fundamental understanding of mRNA vaccine:host interactions and immune functions driving the quality of responses is largely lacking. This proposal focuses on exploring such mechanisms.

We will use rhesus macaques to evaluate vaccine biodistribution, antigen production and innate immune activation in vivo. Some of these aspects will also be analyzed in human samples early after mRNA vaccination.

We will then study the development of B cell responses including germinal center formation and expansion of clonal repertoires.

We will analyze whether vaccines against the same antigen given as an mRNA vaccine vs protein or inactivated virus vaccine induce immunity of different quality.

Importantly, we will compare responses between vaccines in the elderly where there is a high demand on the vaccine:host interaction to induce protective responses.

State-of-the art techniques to characterize vaccine-specific B cells will be used for sequence analysis, expression of antibodies and functional testing.

More knowledge about how the immune system reacts to different vaccines will help select and develop effective but safe vaccines.