Understanding the Fate of mRNA Vaccines in vivo and Mechanisms of Early Responses

The innate mechanisms priming vaccine responses and why different vaccine formulations induce quantitatively and qualitatively different responses are largely unknown, yet represent a fundamental element in vaccinology. Many of the basic mechanisms by which mRNA vaccines induce strong responses are incompletely understood. We have established a non-human primate (NHP) model to in vivo illustrate the first immune processes after mRNA vaccine administration. By using fluorescently-labelled and encoding vaccines we can track the biodistribution and cell specific targeting after delivery as well as recruitment of cells to the site of injection, local activation profiles and priming of T cell and B cell responses. In addition, different delivery routes can be compared. As there is much resemblance in immune cell subsets and innate pathways between NHPs and humans, this is a powerful model for studies of how vaccines may work in humans. A clinical study in healthy individuals receiving SARS-CoV-2 mRNA vaccination was performed to study the innate immune responses and links to the quality and durability of antibodies. In summary, this type of data can help in the understanding of innate immune mechanisms shaping vaccine responses and be used for optimizing future vaccine formulations and delivery.