tetano
Editor, Senior Moderator
Clin Pharmacol Ther
. 2022 Nov 15.
doi: 10.1002/cpt.2796. Online ahead of print.
Quantifying Antibody Persistence After a Single Dose of COVID-19 Vaccine Ad26.COV2.S in Humans Using a Mechanistic Modeling and Simulation Approach
Anna Dari[SUP] 1 [/SUP], Muriel Boulton[SUP] 1 [/SUP], Martine Neyens[SUP] 1 [/SUP], Mathieu Le Gars[SUP] 2 [/SUP], Belén Valenzuela[SUP] 3 [/SUP], Georgi Shukarev[SUP] 2 [/SUP], Vicky Cárdenas[SUP] 4 [/SUP], Javier Ruiz-Guiñazú[SUP] 1 [/SUP], Jerald Sadoff[SUP] 2 [/SUP], Richard M W Hoetelmans[SUP] 1 [/SUP], Juan José Pérez Ruixo[SUP] 1 [/SUP]
Affiliations
Abstract
Understanding persistence of humoral immune responses elicited by vaccination against coronavirus disease (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 1185 S-ELISA titers from 82 and 220 participants, respectively, were analyzed following administration of a single dose of Ad26.COV2.S (5 × 10[SUP]10[/SUP] 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 females relative to males. A steeper waning of antibody responses was predicted in males and in older adults.
. 2022 Nov 15.
doi: 10.1002/cpt.2796. Online ahead of print.
Quantifying Antibody Persistence After a Single Dose of COVID-19 Vaccine Ad26.COV2.S in Humans Using a Mechanistic Modeling and Simulation Approach
Anna Dari[SUP] 1 [/SUP], Muriel Boulton[SUP] 1 [/SUP], Martine Neyens[SUP] 1 [/SUP], Mathieu Le Gars[SUP] 2 [/SUP], Belén Valenzuela[SUP] 3 [/SUP], Georgi Shukarev[SUP] 2 [/SUP], Vicky Cárdenas[SUP] 4 [/SUP], Javier Ruiz-Guiñazú[SUP] 1 [/SUP], Jerald Sadoff[SUP] 2 [/SUP], Richard M W Hoetelmans[SUP] 1 [/SUP], Juan José Pérez Ruixo[SUP] 1 [/SUP]
Affiliations
- PMID: 36377532
- DOI: 10.1002/cpt.2796
Abstract
Understanding persistence of humoral immune responses elicited by vaccination against coronavirus disease (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 1185 S-ELISA titers from 82 and 220 participants, respectively, were analyzed following administration of a single dose of Ad26.COV2.S (5 × 10[SUP]10[/SUP] 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 females relative to males. A steeper waning of antibody responses was predicted in males and in older adults.