Exponential decline, ceiling effect, downregulation, and T-cell response in immunoglobulin G antibody levels after...

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.

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.

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.