Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report

Abstract Background Vaccine protection against severe acute respiratory syndrome coronavirus 2 infection reduces gradually over time, requiring administration of updated boosters. However, long-term immune response following up to the sixth dose of the messenger RNA vaccine has not been well studied...

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Main Authors: Harukazu Hirano, Hiroshi Asada
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Journal of Medical Case Reports
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Online Access:https://doi.org/10.1186/s13256-024-04889-2
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author Harukazu Hirano
Hiroshi Asada
author_facet Harukazu Hirano
Hiroshi Asada
author_sort Harukazu Hirano
collection DOAJ
description Abstract Background Vaccine protection against severe acute respiratory syndrome coronavirus 2 infection reduces gradually over time, requiring administration of updated boosters. However, long-term immune response following up to the sixth dose of the messenger RNA vaccine has not been well studied. Case presentation We longitudinally determined anti-spike protein immunoglobulin G antibody levels in a 69-year-old Japanese man 76 times (first to sixth dose) to investigate their dynamics. Regarding the messenger RNA BNT162b2 vaccine, first to fourth doses were identical monovalent vaccines, and fifth and sixth doses were identical bivalent vaccines. T-cell responses after fourth and fifth doses were studied using T-SPOT. Immunoglobulin G levels peaked at 1–2 weeks after second to sixth dose, declining exponentially after each dose. The decline was approximated using the formula f (t) = Ae−t/τ  + C. Time constant τ increased with each booster vaccination, indicating a decreasing rate of antibody titer decay with increasing number of doses. Baseline and peak immunoglobulin G levels were similar in the second and third dose. Conversely, baseline immunoglobulin G levels after the fourth dose increased over fivefold over the second and third dose; however, peak immunoglobulin G levels after fourth dose decreased to 60% of those after the third dose. Baseline immunoglobulin G levels after the sixth dose increased 1.4-fold over the fifth dose; however, peak immunoglobulin G levels after the sixth dose decreased to 56% of those after the fifth dose. Dynamics of T-cell responses differed from those of immunoglobulin G antibodies. T cell responses increased gradually; however, their peak level was difficult to determine. Conclusions Ceiling effect or downregulation of peak immunoglobulin G levels was clearly observed after messenger RNA booster vaccination. After peaking, the IgG level declined exponentially, and the rate of decay decreased with each subsequent booster. Although this was a single-case study, this data may provide a generalized mathematical decay model for humoral immunity in healthy older adults. Moreover, our study provides insights into the immunogenicity after booster vaccination with messenger RNA vaccines.
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spelling doaj-art-9e7933f5dcd640cf826d2f18f10e79ae2025-08-20T02:39:40ZengBMCJournal of Medical Case Reports1752-19472024-12-011811910.1186/s13256-024-04889-2Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case reportHarukazu Hirano0Hiroshi Asada1Koyo Seikyo Clinic, Fukui Health Cooperative AssociationDepartment of Applied Physics, Faculty of Engineering, University of FukuiAbstract Background Vaccine protection against severe acute respiratory syndrome coronavirus 2 infection reduces gradually over time, requiring administration of updated boosters. However, long-term immune response following up to the sixth dose of the messenger RNA vaccine has not been well studied. Case presentation We longitudinally determined anti-spike protein immunoglobulin G antibody levels in a 69-year-old Japanese man 76 times (first to sixth dose) to investigate their dynamics. Regarding the messenger RNA BNT162b2 vaccine, first to fourth doses were identical monovalent vaccines, and fifth and sixth doses were identical bivalent vaccines. T-cell responses after fourth and fifth doses were studied using T-SPOT. Immunoglobulin G levels peaked at 1–2 weeks after second to sixth dose, declining exponentially after each dose. The decline was approximated using the formula f (t) = Ae−t/τ  + C. Time constant τ increased with each booster vaccination, indicating a decreasing rate of antibody titer decay with increasing number of doses. Baseline and peak immunoglobulin G levels were similar in the second and third dose. Conversely, baseline immunoglobulin G levels after the fourth dose increased over fivefold over the second and third dose; however, peak immunoglobulin G levels after fourth dose decreased to 60% of those after the third dose. Baseline immunoglobulin G levels after the sixth dose increased 1.4-fold over the fifth dose; however, peak immunoglobulin G levels after the sixth dose decreased to 56% of those after the fifth dose. Dynamics of T-cell responses differed from those of immunoglobulin G antibodies. T cell responses increased gradually; however, their peak level was difficult to determine. Conclusions Ceiling effect or downregulation of peak immunoglobulin G levels was clearly observed after messenger RNA booster vaccination. After peaking, the IgG level declined exponentially, and the rate of decay decreased with each subsequent booster. Although this was a single-case study, this data may provide a generalized mathematical decay model for humoral immunity in healthy older adults. Moreover, our study provides insights into the immunogenicity after booster vaccination with messenger RNA vaccines.https://doi.org/10.1186/s13256-024-04889-2BNT162b2AntibodyT-SPOTCeiling effect
spellingShingle Harukazu Hirano
Hiroshi Asada
Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report
Journal of Medical Case Reports
BNT162b2
Antibody
T-SPOT
Ceiling effect
title Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report
title_full Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report
title_fullStr Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report
title_full_unstemmed Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report
title_short Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after messenger RNA vaccine boosters: a case report
title_sort exponential decline ceiling effect downregulation and t cell response in immunoglobulin g antibody levels after messenger rna vaccine boosters a case report
topic BNT162b2
Antibody
T-SPOT
Ceiling effect
url https://doi.org/10.1186/s13256-024-04889-2
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