Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Department of Microbiology, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Microbiol Spectr. 2021 Dec 22;9(3):e0056121. doi: 10.1128/Spectrum.00561-21. Epub 2021 Dec 1.
Vaccines against severe acute respiratory syndrome coronavirus-2 have been introduced. To investigate the relationship between vaccine-induced humoral immunity and patient age, we measured antibody levels and neutralization in vaccinated sera. Sera from 13 to 17 days after the second dose of the BNT162b2 vaccine were collected from health care workers at the University of Toyama ( = 740). Antibody levels were measured by the anti-receptor binding domain antibody test (anti-RBD test), and neutralization against wild-type (WT), α- and β-variant pseudotyped viruses were assayed using a high-throughput chemiluminescent reduction neutralizing test (htCRNT; positivity cutoff, 50% neutralization at serum dilution 1:100). Basic clinical characteristics were obtained from questionnaires. Antibodies were confirmed in all participants in both the anti-RBD test (median, 2,112 U/ml; interquartile range [IQR], 1,275 to 3,390 U/ml) and the htCRNT against WT (median % inhibition, >99.9; IQR, >99.9 to >99.9). For randomly selected sera ( = 61), 100.0% had positive htCRNT values against the α- and β-derived variants. Among those who answered the questionnaire ( = 237), the values of the anti-RBD test were negatively correlated with age in females ( < 0.01). An age-dependent decline in neutralization was observed against the variants but not against the wild-type virus (wild type, = 0.09; α, < 0.01; β, < 0.01). The neutralizing activity induced by BNT162b2 was obtained not only against the wild-type virus, but also against the variants; however, there was an age-dependent decrease in the latter. Age-related heterogeneity of vaccine-acquired immunity is a concern in preventive strategies in the era dominated by variants. Since mRNA vaccines utilize wild-type SARS-CoV-2 spike protein as an antigen, there are potential concerns about acquiring immunity to variants of this virus. The neutralizing activity in BNT162b2-vaccinated individuals was higher against the wild-type virus than against its variants; this effect was more apparent in older age groups. This finding suggests that one of the weaknesses of the mRNA vaccine is the high risk of variant infection in the elderly population. Because the elderly are at a higher risk of SARS-CoV-2 infection, the age-dependent decline of neutralization against viral variants should be considered while planning vaccination programs that include boosters.
已推出针对严重急性呼吸综合征冠状病毒 2 的疫苗。为了研究疫苗诱导的体液免疫与患者年龄之间的关系，我们测量了接种疫苗血清中的抗体水平和中和作用。从富山大学的医护人员接种 BNT162b2 疫苗后 13 至 17 天采集血清（ = 740）。通过抗受体结合域抗体检测（anti-RBD test）测量抗体水平，并使用高通量化学发光减少中和试验（htCRNT）检测针对野生型（WT）、α-和 β-变体假型病毒的中和作用（阳性截断值，血清稀释度为 1:100 时的 50%中和）。从问卷调查中获得基本临床特征。在 anti-RBD 检测（中位数 2,112 U/ml；四分位距 [IQR] 1,275 至 3,390 U/ml）和针对 WT 的 htCRNT 中（中位数抑制百分比>99.9；IQR>99.9 至>99.9），所有参与者的抗体均得到确认。对于随机选择的血清（ = 61），针对 α-和 β-衍生变体，100.0%的 htCRNT 值为阳性。在回答问卷的人群中（ = 237），女性的 anti-RBD 检测值与年龄呈负相关（<0.01）。针对变体的中和作用呈年龄依赖性下降，但针对野生型病毒则无此情况（野生型，<0.01；α，<0.01；β，<0.01）。BNT162b2 诱导的中和活性不仅针对野生型病毒，而且针对变体；然而，后者的活性随年龄增长而下降。在以变体为主导的时代，疫苗获得的免疫的年龄相关性异质性令人担忧。由于 mRNA 疫苗将野生型 SARS-CoV-2 刺突蛋白用作抗原，因此人们对获得该病毒变体的免疫力存在潜在担忧。在 BNT162b2 疫苗接种个体中，针对野生型病毒的中和活性高于针对其变体的中和活性；在年龄较大的人群中，这种作用更为明显。这一发现表明，mRNA 疫苗的一个弱点是老年人感染病毒变体的风险较高。由于老年人感染 SARS-CoV-2 的风险较高，在规划包括加强针在内的疫苗接种计划时，应考虑针对病毒变体的中和作用随年龄下降的问题。
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