Matei Lilia, Chivu-Economescu Mihaela, Dragu Laura Denisa, Grancea Camelia, Bleotu Coralia, Hrișcă Raluca, Popescu Corneliu Petru, Diaconu Carmen C, Ruţă Simona Maria
Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania.
Romanian Academy Doctoral School, 010071 Bucharest, Romania.
Int J Mol Sci. 2025 Aug 21;26(16):8106. doi: 10.3390/ijms26168106.
There is an increasing need to understand the long-term dynamics and quality of SARS-CoV-2 immune memory-both humoral and cellular-particularly with emerging variants. This study aimed to evaluate immune durability and variant-specific modulation through a longitudinal analysis of individuals with diverse SARS-CoV-2 exposure histories, over two years after infection and/or vaccination. The study involved assessing anti-spike IgG and IgA levels over time and analyzing their relationship with neutralizing activity against both ancestral and Omicron SARS-CoV-2 variants. Persistence of T cell responses was evaluated using intracellular cytokine staining (ICS) and activation-induced marker (AIM) assays. Anti-S IgG levels remained stable over time and increased after each immune stimulation, suggesting cumulative immune memory. Neutralizing capacity correlated strongly with IgG levels, showing long-term stability for pre-Omicron variants, but a moderate decline for Omicron. CD4 and CD8 T cell responses persisted across all groups, largely unaffected by Omicron mutations. However, cytokine profiles revealed subtle, variant-dependent changes. These findings underscore the durability of cellular immunity and the comparatively reduced robustness of Omicron-specific humoral responses. Such insights are crucial for understanding long-term protection against evolving SARS-CoV-2 variants and guiding public health strategies.
越来越有必要了解严重急性呼吸综合征冠状病毒2（SARS-CoV-2）免疫记忆的长期动态和质量，包括体液免疫和细胞免疫，尤其是针对新出现的变异株。本研究旨在通过对具有不同SARS-CoV-2暴露史的个体在感染和/或接种疫苗两年后的纵向分析，评估免疫持久性和变异株特异性调节。该研究包括随时间评估抗刺突IgG和IgA水平，并分析它们与针对原始株和奥密克戎株SARS-CoV-2变异株的中和活性之间的关系。使用细胞内细胞因子染色（ICS）和激活诱导标志物（AIM）检测评估T细胞反应的持久性。抗S IgG水平随时间保持稳定，并在每次免疫刺激后升高，表明存在累积免疫记忆。中和能力与IgG水平密切相关，对于奥密克戎变异株出现之前的变异株显示出长期稳定性，但对奥密克戎变异株则有适度下降。CD4和CD8 T细胞反应在所有组中均持续存在，很大程度上不受奥密克戎突变的影响。然而，细胞因子谱显示出细微的、依赖于变异株的变化。这些发现强调了细胞免疫的持久性以及奥密克戎特异性体液反应相对较低的稳健性。这些见解对于理解针对不断演变的SARS-CoV-2变异株的长期保护以及指导公共卫生策略至关重要。
