Quantifying Antibody Persistence After a Single Dose of COVID‐19 Vaccine Ad26.COV2.S in Humans Using a Mechanistic Modeling and Simulation Approach

Understanding persistence of humoral immune responses elicited by vaccination against coronavirus disease 2019 (COVID‐19) is critical for informing the duration of protection and appropriate booster timing. We developed a mechanistic model to characterize the time course of humoral immune responses in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)–seronegative adults after primary vaccination with the Janssen COVID‐19 vaccine, Ad26.COV2.S. The persistence of antibody responses was quantified through mechanistic modeling‐based simulations. Two biomarkers of humoral immune responses were examined: SARS‐CoV‐2 neutralizing antibodies determined by wild‐type virus neutralization assay (wtVNA) and spike protein‐binding antibodies determined by indirect spike protein enzyme‐linked immunosorbent assay (S‐ELISA). The persistence of antibody responses was defined as the period of time during which wtVNA and S‐ELISA titers remained above the lower limit of quantification. A total of 442 wtVNA and 1,185 S‐ELISA titers from 82 and 220 participants, respectively, were analyzed following administration of a single dose of Ad26.COV2.S (5 × 10(10) viral particles). The mechanistic model adequately described the time course of observed wtVNA and S‐ELISA serum titers and its associated variability up to 8 months following vaccination. Mechanistic model‐based simulations show that single‐dose Ad26.COV2.S elicits durable but waning antibody responses up to 24 months following immunization. Of the estimated model parameters, the production rate of memory B cells was decreased in older adults relative to younger adults, and the antibody production rate mediated by long‐lived plasma cells was increased in women relative to men. A steeper waning of antibody responses was predicted in men and in older adults.