Pisil Yalcin, Miura Tomoyuki, Ito Kiyoki, Watanabe Yoshihiro
Laboratory of Primate Model, Research Center for Infectious Diseases, Institute for Life and Medical Science, Kyoto University, Kyoto 615-8530, Japan.
Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-0934, Japan.
Antibodies (Basel). 2025 Jul 12;14(3):59. doi: 10.3390/antib14030059.
The durability and breadth of neutralizing antibodies following SARS-CoV-2 mRNA vaccination remain incompletely understood. This study aimed to investigate how longitudinal changes in antibody isotype composition impact neutralization against structurally diverse SARS-CoV-2 variants. After screening a broader cohort of mRNA-vaccinated sera, time-matched samples collected one month (1 mpv) and three months post-vaccination (3 mpv) were selected for detailed analysis. Neutralization assays against live virus variants, enzyme-linked immunosorbent assays (ELISA), and immunogold electron microscopy were performed to assess antibody titers, isotype levels, and virion morphology. Neutralization titers declined markedly at 3 mpv, particularly against immune-evasive variants. Notably, the Lambda variant showed disproportionately high sensitivity to early-phase sera despite its divergence from the vaccine strain. Antibody isotyping showed that IgA and IgM decreased over time, while IgG levels were relatively more sustained. Electron microscopy revealed broader virion size heterogeneity in Lambda (50-200 nm) compared to Wuhan (80-120 nm), potentially enhancing multivalent antibody engagement. Consistently, ELISA under reduced spike density conditions showed that IgA and IgM retained stronger binding than IgG. These findings indicate that the decline of IgA and IgM compromises neutralization breadth, especially against structurally divergent variants such as Lambda. Sustaining dynamic multivalent isotype responses that adapt to diverse spike morphologies may be critical for broad cross-variant immunity.
SARS-CoV-2 mRNA疫苗接种后中和抗体的持久性和广度仍未完全了解。本研究旨在调查抗体亚型组成的纵向变化如何影响对结构多样的SARS-CoV-2变体的中和作用。在筛选了更广泛的mRNA疫苗接种血清队列后，选择接种疫苗后1个月（1 mpv）和3个月（3 mpv）采集的时间匹配样本进行详细分析。对活病毒变体进行中和试验、酶联免疫吸附试验（ELISA）和免疫金电子显微镜检查，以评估抗体滴度、亚型水平和病毒粒子形态。中和滴度在3 mpv时显著下降，尤其是针对免疫逃逸变体。值得注意的是，尽管Lambda变体与疫苗株存在差异，但它对早期血清表现出异常高的敏感性。抗体亚型分析表明，IgA和IgM随时间下降，而IgG水平相对更稳定。电子显微镜显示，与武汉株（80-120 nm）相比，Lambda变体的病毒粒子大小异质性更广泛（50-200 nm），这可能增强多价抗体的结合。一致地，在降低刺突密度条件下的ELISA表明，IgA和IgM比IgG保留更强的结合力。这些发现表明，IgA和IgM的下降会损害中和广度，尤其是针对结构不同的变体，如Lambda。维持适应不同刺突形态的动态多价亚型反应可能对广泛的交叉变体免疫至关重要。
