A clinically parameterized mathematical model of Shigella immunity to inform vaccine design

We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge agai...