Immunostimulatory/immunodynamic model of mRNA-1273 to guide pediatric vaccine dose selection

COVID-19 vaccines, including mRNA-1273, have been rapidly developed and deployed. To develop a safe and effective vaccine, establishing the optimal dose is crucial, and is where modeling and simulation can be used to guide vaccine dose selection and development. We developed an immunostimulatory/immunodynamic (IS/ID) model to quantitatively characterize the neutralizing antibody titers elicited by mRNA-1273 obtained from three clinical studies and to predict the optimal vaccine dose for future pediatric trials. A 25-µg primary vaccine series was predicted to meet non-inferiority criteria in young children (aged 2-5 years) and infants (aged 6-23 months); geometric mean titers and geometric mean ratios for this dose level predicted using the IS/ID model a priori matched those observed in the pediatric clinical study. These findings demonstrate that IS/ID models represent a novel approach to guide data-driven clinical dose selection of vaccines.