Hirano Harukazu, Asada Hiroshi
Koyo Seikyo Clinic, Fukui Health Cooperative Association, 3-9-23 Koyo, Fukui, 910-0026, Japan.
Department of Applied Physics, Faculty of Engineering, University of Fukui, 3-9-1 Bunkyo, Fukui, 910-8507, Japan.
J Med Case Rep. 2024 Dec 20;18(1):631. doi: 10.1186/s13256-024-04889-2.
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 + 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.
针对严重急性呼吸综合征冠状病毒2感染的疫苗保护作用会随着时间逐渐减弱，需要接种更新的加强针。然而，接种信使核糖核酸疫苗第六剂后的长期免疫反应尚未得到充分研究。
我们纵向测定了一名69岁日本男性接种信使核糖核酸疫苗76次（第一剂至第六剂）后的抗刺突蛋白免疫球蛋白G抗体水平，以研究其动态变化。对于信使核糖核酸BNT162b2疫苗，第一剂至第四剂为相同的单价疫苗，第五剂和第六剂为相同的二价疫苗。使用T-SPOT研究第四剂和第五剂后的T细胞反应。免疫球蛋白G水平在第二剂至第六剂接种后1至2周达到峰值，每次接种后呈指数下降。使用公式f (t) = Ae + C近似计算下降情况。时间常数τ随着每次加强接种而增加，表明抗体滴度衰减率随着接种剂量的增加而降低。第二剂和第三剂的基线和峰值免疫球蛋白G水平相似。相反，第四剂后的基线免疫球蛋白G水平比第二剂和第三剂增加了五倍多；然而，第四剂后的峰值免疫球蛋白G水平降至第三剂后的60%。第六剂后的基线免疫球蛋白G水平比第五剂增加了1.4倍；然而，第六剂后的峰值免疫球蛋白G水平降至第五剂后的56%。T细胞反应的动态变化与免疫球蛋白G抗体不同。T细胞反应逐渐增加；然而，其峰值水平难以确定。
在信使核糖核酸加强接种后，明显观察到了免疫球蛋白G峰值水平的天花板效应或下调。达到峰值后，IgG水平呈指数下降，且每次后续加强接种后的衰减率降低。虽然这是一项单病例研究，但这些数据可能为健康老年人的体液免疫提供一个通用的数学衰减模型。此外，我们的研究为信使核糖核酸疫苗加强接种后的免疫原性提供了见解。
