Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
Front Immunol. 2024 Mar 12;15:1340645. doi: 10.3389/fimmu.2024.1340645. eCollection 2024.
The 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.
We 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.
We 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.
Reduction 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.
SARS-CoV-2 变体的出现引发了人们对疫苗诱导免疫可持续性的担忧。关于奥密克戎变体的长期体液反应和刺突特异性 T 细胞记忆，我们知之甚少，特别是针对 BA.4/5、BQ.1.1 和 XBB.1。
我们评估了 50 名未感染个体在接种三剂疫苗（2X 阿斯利康+1X 莫德纳、1X 阿斯利康+2X 莫德纳和 3X 莫德纳）后八个月对野生型（WT）和奥密克戎变体的免疫反应。通过酶联免疫吸附试验（ELISA）分析血清抗体滴度，通过假病毒和感染性 SARS-CoV-2 中和试验检测中和活性。通过流式细胞术测定 T 细胞反应性及其记忆表型。
我们发现与 WT 相比，针对奥密克戎变体的 RBD 特异性抗体滴度、中和活性和 CD4+T 细胞反应性降低。相比之下，在刺激奥密克戎肽库时，CD8+T 细胞反应、中央记忆、效应记忆和 CD45RA+效应记忆 T 细胞不受影响。值得注意的是，CD4+效应记忆 T 细胞甚至对奥密克戎变体表现出更高比例的反应性。此外，接受三剂 Moderna 的参与者在中和和 CD8+T 细胞反应方面的反应比其他三剂疫苗接种组更强烈。
接种者对奥密克戎变体的体液和 CD4+T 细胞反应性降低表明，八个月后疫苗的有效性可能无法提供对新出现变体的充分保护，这为未来的疫苗接种策略提供了有价值的信息，例如接种 BA.4/5 或 XBB.1 基于二价疫苗。
