Table_1_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变种的涌现引发了人们对疫苗接种诱导的免疫可持续性的担忧。关于Omicron变种（特别是BA.4/5、BQ.1.1和XBB.1）的长期体液反应和针对刺突蛋白的T细胞记忆，知之甚少。方法：我们评估了50名未感染个体在疫苗接种后八个月针对野生型（WT）和Omicron变种所接受的多种三剂疫苗接种组合（2次阿斯利康+1次莫德纳，1次阿斯利康+2次莫德纳，以及3次莫德纳）的免疫反应。通过酶联免疫吸附测定（ELISA）分析了血清抗体滴度，并通过假病毒和感染性SARS-CoV-2中和试验考察了中和活性。利用流式细胞术确定了T细胞反应及其记忆表型。结果：我们发现，与WT相比，针对Omicron变种的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，CD8+ T细胞反应、中央记忆、效应记忆以及CD45RA+效应记忆T细胞在Omicron多肽池的刺激下保持未受影响。值得注意的是，CD4+效应记忆T细胞甚至在对Omicron变种的反应中显示出更高的反应比例。此外，接受三剂莫德纳疫苗接种的参与者，在中和和CD8+ T细胞反应方面表现出比其他三剂疫苗接种组更为强劲的反应。结论：疫苗接种者对Omicron变种的体液和CD4+ T细胞反应的降低表明，疫苗接种八个月后的疫苗效力可能不足以对新兴变种提供充分的保护，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）提供了宝贵的信息。