Beyond the injection site: identifying the cellular targets of mRNA vaccines

Abstract

Vaccines against COVID-19 based on the mRNA technology have broken many records, from the speed of development and production, to the number of doses administered and have overall proven safe, with only very rare reported adverse events. The accelerated rollout and the permissive regulatory framework had the major caveat that manufacturers did not provide biodistribution and pharmacokinetics data for their products in humans, despite this being essential for interpreting both the dynamics of the immune response and any potential toxic effects. Thankfully, in the past two years, the scientific community has attempted to fill the gaps, which will undoubtedly help in fine-tuning the next generation of mRNA vaccines. Here we review existing data on the biodistribution and pharmacokinetics of the commercially available mRNA vaccine platforms, focusing on human studies, where available. We structure this review by tissue type and we discuss potential correlations between vaccine mRNA uptake and pathogenic effects, if applicable. We find that many studies have focused on the heart, due to the medical and social impact of myocarditis, especially in adolescents. We conclude by observing critical data is still missing for many organs and we suggest potential avenues for future research.