Department of Medicine, Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada.
Clin Infect Dis. 2023 Jul 26;77(2):229-236. doi: 10.1093/cid/ciad175.
In solid organ transplant (SOT) recipients, the primary vaccination series against Coronavirus Disease 2019 is 3 doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies (nAbs) and T cells in a large multicenter cohort study.
Serum was collected 4-6 weeks post-third and post-fourth doses of messenger RNA vaccine in 222 SOT recipients. nAbs were measured using a pseudovirus neutralization assay that targeted the Omicron BA.4/5 spike protein. A subset underwent T-cell testing.
The median age of the cohort was 63 years (interquartile range [IQR], 50-68) with 61.7% men. BA.4/5 nAb detection increased from 26.6% (59 of 222) post-third dose to 53.6% (119 of 222) post-fourth dose (P < .0001). In patients with breakthrough infection prior to the fourth dose (n = 27), nAbs were detected in 77.8% and median nAb titers were significantly higher compared with those with 4 vaccine doses alone (P < .0001). Factors associated with a low BA.4/5 neutralization response after the fourth dose were older age (odds ratio [OR], 0.96; 95% confidence interval [CI], .94-.99), mycophenolate use (OR, 0.39; 95% CI, .20-.77) and prednisone use (OR, 0.34; 95% CI, .18-.63), and vaccine type (OR, 0.72; 95% CI, .51-.99), while breakthrough infection prior to the fourth dose (OR, 3.6; 95% CI, 1.3-9.9) was associated with a greater nAb response. Polyfunctional BA.4/5-specific CD4+ T cells significantly increased after 4 doses and were identified in 76.9% of patients at a median frequency of 213/106 cells (IQR, 98-650).
In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients who are older and on mycophenolate and prednisone need additional preventative strategies.
在实体器官移植（SOT）受者中，针对 2019 年冠状病毒病的初级疫苗接种系列为 3 剂，随后进行加强针接种。我们在一项大型多中心队列研究中确定了第四剂加强针是否会诱导针对奥密克戎 BA.4/5 的中和抗体（nAbs）和 T 细胞。
在 222 名 SOT 受者中，在第三次和第四次接种信使 RNA 疫苗后 4-6 周采集血清。使用针对奥密克戎 BA.4/5 刺突蛋白的假病毒中和测定法测量 nAbs。一部分患者接受了 T 细胞检测。
队列的中位年龄为 63 岁（四分位距[IQR]，50-68），其中 61.7%为男性。BA.4/5 nAb 的检出率从第三次剂量后的 26.6%（222 例中的 59 例）增加到第四次剂量后的 53.6%（222 例中的 119 例）（P <.0001）。在第四次剂量前发生突破性感染的患者（n = 27）中，77.8%检测到 nAbs，与仅接种 4 剂疫苗的患者相比，中位 nAb 滴度显著更高（P <.0001）。第四次剂量后 BA.4/5 中和反应较低的相关因素包括年龄较大（优势比[OR]，0.96；95%置信区间[CI]，0.94-0.99）、使用吗替麦考酚酯（OR，0.39；95%CI，0.20-0.77）和使用泼尼松（OR，0.34；95%CI，0.18-0.63），以及疫苗类型（OR，0.72；95%CI，0.51-0.99），而第四次剂量前发生突破性感染（OR，3.6；95%CI，1.3-9.9）与更高的 nAb 反应相关。第四次剂量后，BA.4/5 特异性 CD4+ T 细胞的多能性显著增加，在 76.9%的患者中以中位数频率 213/106 细胞（IQR，98-650）检出。
总之，加强针显著增加了 BA.4/5 特异性中和和多能性 CD4+ T 细胞反应，表明即使出现新的奥密克戎变异株，也能提供对严重疾病的保护。然而，年龄较大且使用吗替麦考酚酯和泼尼松的 SOT 受者需要额外的预防策略。
