Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity against original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1–10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and P.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.

随着时间的推移，针对 SARS-CoV-2 的抗体滴度逐渐下降。在这里，我们研究了时间如何影响抗体效力。为了评估抗体成熟对原始 SARS-CoV-2 和新出现的关注变异 (VOC) 的持久中和活性的影响，我们分析了 SARS 后 1-10 个月恢复期血浆中的受体结合域 (RBD) 特异性 IgG 抗体- CoV-2感染。对总 RBD IgG 和中和抗体的纵向评估显示，总抗体滴度下降，但每个抗体对原始 SARS-CoV-2 的中和效力提高，表明抗体反应成熟。用真实病毒进行的中和试验表明，能够中和原始 SARS-CoV-2 的早期抗体对 B.1.351 (501Y.V2) 和 P.1 (501Y.V3) 变体的反应性有限。晚期康复者的抗体对 VOC 的中和能力增强，表明血浆中存在交叉中和抗体。因此，对 SARS-CoV-2 抗体反应的成熟增强了对循环变异体的交叉中和能力，这表明抗体滴度下降可能并不表示保护作用下降。