Speaker
Description
Antibody response dynamics following Ebola vaccination remain incompletely understood, particularly regarding the continuum of initial induction to long-term persistence. This study developed a mechanistic model of B-cell stimulation post-vaccination able to infer antigen presentation kinetics and propose an identifiable model based solely on anti-ZEBOV IgG levels.
This study was based on the PREVAC randomized placebo-controlled trial (NCT02876328), which enrolled healthy adults and children to evaluate three vaccine strategies: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26–MVA group, 799 participants), rVSV∆G-ZEBOV-GP followed by placebo 56 days later (the rVSV group, 802 participants), and rVSV∆G-ZEBOV-GP followed by rVSV∆G-ZEBOV- GP 56 days later (the rVSV–booster group, 399 participants). Our model was modified from Clairon et al. (2022, PLOS Comp. Biol.), which assumes that antigen stimulates the
differentiation of naive B cells into long-lived and short-lived antibody-secreting cells. We compared vaccine exposure using a decreasing exponential or a bell-shaped curve. Parameters were derived from literature on vaccine viremia and distribution or estimated using data-driven approaches.
For both vaccine groups, a bell-shaped curve best described the dynamics according to model information criterion (BICc) indicating a long antigen presentation regardless of vaccine replication competence. Longer presentation times were found for rVSV (half-life t1/2=6.9 days at first dose and t1/2=0.07 days at second dose) than for Ad26–MVA (t1/2=2.77 days for Ad26.ZEBOV and t1/2=1.39 days for MVA-BN-Filo). Overall fits showed good adjustment but usually underestimated peak antibody concentrations, especially in the highest responders. We also demonstrated that sociodemographics such as sex, age and country of residence has a significant impact on the humoral dynamics.
While our model is one of the first attempts to better understand antigen presentation kinetics, this study shows limitations due to limited observation of B cell responses. It however constitutes an in silico platform to emulate personalized scheme for optimized Ebola late vaccination according to sociodemographics.
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