Table_3_Long-term analysis of humoral responses and spike-specific T cell memory to Omicron variants after different COVID-19 vaccine regimens.docx

BackgroundThe emergence of SARS-CoV-2 variants has raised concerns about the sustainability of vaccine-induced immunity. Little is known about the long-term humoral responses and spike-specific T cell memory to Omicron variants, with specific attention to BA.4/5, BQ.1.1, and XBB.1.MethodsWe assessed immune responses in 50 uninfected individuals who received varying three-dose vaccination combinations (2X AstraZeneca + 1X Moderna, 1X AstraZeneca + 2X Moderna, and 3X Moderna) against wild-type (WT) and Omicron variants at eight months post-vaccination. The serum antibody titers were analyzed by enzyme-linked immunosorbent assays (ELISA), and neutralizing activities were examined by pseudovirus and infectious SARS-CoV-2 neutralization assays. T cell reactivities and their memory phenotypes were determined by flow cytometry.ResultsWe found that RBD-specific antibody titers, neutralizing activities, and CD4+ T cell reactivities were reduced against Omicron variants compared to WT. In contrast, CD8+ T cell responses, central memory, effector memory, and CD45RA+ effector memory T cells remained unaffected upon stimulation with the Omicron peptide pool. Notably, CD4+ effector memory T cells even exhibited a higher proportion of reactivity against Omicron variants. Furthermore, participants who received three doses of the Moderna showed a more robust response regarding neutralization and CD8+ T cell reactions than other three-dose vaccination groups.ConclusionReduction of humoral and CD4+ T cell responses against Omicron variants in vaccinees suggested that vaccine effectiveness after eight months may not have sufficient protection against the new emerging variants, which provides valuable information for future vaccination strategies such as receiving BA.4/5 or XBB.1-based bivalent vaccines.

背景：SARS-CoV-2 变异株的出现引发了人们对疫苗诱导免疫持久性的担忧。关于 Omicron 变异株（特别是 BA.4/5、BQ.1.1 和 XBB.1）的长期体液免疫反应和针对刺突蛋白的 T 细胞记忆，目前所知甚少。方法：我们评估了 50 名未感染者在疫苗接种八个月后，针对野生型（WT）和 Omicron 变异株的免疫反应，这些个体接受了不同的三剂疫苗接种组合（2X 阿斯利康 + 1X 现代疫苗、1X 阿斯利康 + 2X 现代疫苗和 3X 现代疫苗）。通过酶联免疫吸附测定法（ELISA）分析了血清抗体滴度，并利用伪病毒和感染性 SARS-CoV-2 中和测定法检查了中和活性。通过流式细胞术确定了 T 细胞反应及其记忆表型。结果：我们发现，与 WT 相比，针对 Omicron 变异株的 RBD 特异性抗体滴度、中和活性和 CD4+ T 细胞反应均有所降低。相反，在 Omicron 碱基肽库的刺激下，CD8+ T 细胞反应、中心记忆、效应记忆以及 CD45RA+ 效应记忆 T 细胞保持未受影响。值得注意的是，CD4+ 效应记忆 T 细胞甚至表现出更高的针对 Omicron 变异株的反应比例。此外，接受三剂 Moderna 疫苗的参与者在中和反应和 CD8+ T 细胞反应方面显示出比其他三剂疫苗接种组更强劲的免疫反应。结论：疫苗接种者对 Omicron 变异株的体液和 CD4+ T 细胞反应降低表明，八个月后疫苗的有效性可能不足以提供对新兴变异株的充分保护，这一发现为未来的疫苗接种策略（如接种基于 BA.4/5 或 XBB.1 的二价疫苗）提供了宝贵信息。