Mechanistic Model Describing the Time Course of Humoral Immunity Following Ad26.COV2.S Vaccination in Non-Human...

Area of Science:

• Immunology
• Mathematical Modeling
• Vaccinology

Background:

• Understanding vaccine-induced humoral immunity is crucial for developing effective vaccines.
• Mechanistic modeling offers a powerful tool to dissect the dynamics of immune responses.
• Previous studies have explored antibody kinetics, but detailed mechanistic insights into Ad26.COV2.S regimens are needed.

Purpose of the Study:

• To apply a six-compartment mechanistic model to describe the time course of humoral immunity in non-human primates (NHPs) after Ad26.COV2.S vaccination.
• To identify key biologic drivers of antibody production and their contribution to peak and sustained responses.
• To assess the model's adequacy in capturing antibody concentration variability across different vaccination regimens.

Main Methods:

• A six-compartment mechanistic model was developed and fitted to binding antibody concentration data from 56 NHPs.
• NHPs received Ad26.COV2.S via single-dose (1 × 10^11 or 5 × 10^10 viral particles) or two-dose homologous regimens (5 × 10^10 viral particles) at 4 or 8-week intervals.
• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific binding antibody concentrations were measured using ELISA over a 20-week period.

Main Results:

• The mechanistic model adequately described the central tendency and variability of binding antibody concentrations through 20 weeks for all vaccination arms.
• Parameter estimation indicated that antibody production by short-lived cells was a major driver of peak responses, particularly after the second dose.
• Antibody production by long-lived cells was essential for the initial peak and sustained antibody concentrations throughout the 20-week period.

Conclusions:

• Mechanistic modeling effectively describes vaccine-induced humoral immune responses in NHPs.
• Short-lived plasma cells contribute significantly to rapid antibody responses, while long-lived plasma cells ensure sustained immunity.
• These findings advance our understanding of Ad26.COV2.S immunodynamics and aid in identifying potential immune biomarkers for SARS-CoV-2 protection.