Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
NUS-Cambridge Immune Phenotyping Centre, Life Sciences Institute, National University of Singapore, Singapore.
Immunohorizons. 2023 Oct 1;7(10):708-717. doi: 10.4049/immunohorizons.2300071.
COVID-19 vaccination has significantly impacted the global pandemic by reducing the severity of infection, lowering rates of hospitalization, and reducing morbidity/mortality in healthy individuals. However, the degree of vaccine-induced protection afforded to renal transplant recipients who receive forms of maintenance immunosuppression remains poorly defined. This is particularly important when we factor in the emergence of SARS-CoV-2 variants of concern (VOCs) that have defined mutations that reduce the effectiveness of Ab responses targeting the Spike Ags from the ancestral Wuhan-Hu-1 variants employed in the most widely used vaccine formats. In this study, we describe a qualitative, longitudinal analysis of neutralizing Ab responses against multiple SARS-CoV-2 VOCs in 129 renal transplant recipients who have received three doses of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2). Our results reveal a qualitative and quantitative reduction in the vaccine-induced serological response in transplant recipients versus healthy controls where only 51.9% (67 of 129) made a measurable vaccine-induced IgG response and 41.1% (53 of 129) exhibited a significant neutralizing Ab titer (based on a pseudovirus neutralization test value >50%). Analysis on the VOCs revealed strongest binding toward the wild-type Wuhan-Hu-1 and Delta variants but none with both of the Omicron variants tested (BA1 and BA2). Moreover, older transplant recipients and those who are on mycophenolic acid as part of their maintenance therapy exhibited a profound reduction in all of the analyzed vaccine-induced immune correlates. These data have important implications for how we monitor and manage transplant patients in the future as COVID-19 becomes endemic in our populations.
COVID-19 疫苗接种通过降低感染的严重程度、降低住院率以及降低健康个体的发病率/死亡率，对全球大流行产生了重大影响。然而，接受维持性免疫抑制治疗的肾移植受者接种疫苗所产生的保护程度仍未得到明确界定。当我们考虑到出现了对刺突蛋白 Ags 具有靶向作用的 Ab 反应有效性降低的令人关注的 SARS-CoV-2 变体（VOCs）时，这一点尤为重要。这些变体具有定义明确的突变，而刺突蛋白 Ags 来自我们在最广泛使用的疫苗中使用的原始武汉-汉-1 变体。在这项研究中，我们描述了一项针对 129 名接受三剂辉瑞-生物科技公司的 COVID-19 疫苗（BNT162b2）的肾移植受者针对多种 SARS-CoV-2 VOCs 的中和 Ab 反应的定性、纵向分析。我们的结果揭示了移植受者与健康对照者之间疫苗诱导的血清学反应的定性和定量降低，其中只有 51.9%（129 例中的 67 例）产生了可测量的疫苗诱导 IgG 反应，41.1%（129 例中的 53 例）表现出显著的中和 Ab 滴度（基于假病毒中和试验值>50%）。对 VOCs 的分析表明，与野生型武汉-汉-1 和 Delta 变体的结合最强，但与测试的两种奥密克戎变体（BA1 和 BA2）均无结合。此外，年龄较大的移植受者和那些正在接受吗替麦考酚酯作为其维持治疗一部分的受者，所有分析的疫苗诱导免疫相关性均显著降低。这些数据对于我们在未来如何监测和管理移植患者具有重要意义，因为 COVID-19 在我们的人群中已成为地方病。
