Comprehensive Transplant Center, Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Transpl Infect Dis. 2022 Apr;24(2):e13813. doi: 10.1111/tid.13813. Epub 2022 Mar 3.
Assessing the composition of immune responses to SARS-CoV-2 vaccines is critical for our understanding of protective immunity, especially for immune compromised patients. The Pfizer (BNT162b2) vaccination showed >90% efficacy in protecting individuals from infection. However, these studies did not examine responses in immunocompromised kidney transplant patients (KT). Subsequent reports in KT have shown severe deficiencies in Spike-specific immunoglobin G (IgG) responses prompting booster vaccinations, but a broader understanding of T-cell immunity to vaccinating is lacking.
We examined SARS-CoV-2 Spike IgG and CD4+/CD8+ Spike-specific T-cell responses in 61 KT patients maintained on different immunosuppressive protocols (ISP) (Tac + mycophenolate mofetil + prednisone) versus (belatacept + MMF + prednisone) and compared to 41 healthy controls. We also examined cytomegalovirus-cytotoxic T-cell responses (CMV-Tc) in both groups to assess T-cell memory.
Our data confirmed poor Spike IgG responses in vaccinated KT patients with both ISP (21% demonstrating Spike IgG 1M post-second dose of BNT162b2 vs. 93% in controls). However, 35% of Spike IgG (-) patients demonstrated CD4+ and/or CD8+ T-cell responses. All but one CMV-IgG+ patient demonstrated good CMV-Tc responses. No differences in T-cell immunity by ISP were seen.
Immunocompromised KT recipients showed severe defects in humoral and T-cell immune response after vaccination. No differences in immune responses to SARS-CoV-2 Spike peptides were observed in KT patients by ISP post-vaccination. The detection of Spike-specific T-cell immunity in the absence of Spike IgG suggests that vaccination in immunocompromised KT patients may provide partial immunity, although not preventing infection, T-cell immunity may limit its severity.
评估对 SARS-CoV-2 疫苗的免疫反应组成对于我们理解保护性免疫至关重要，特别是对于免疫功能低下的患者。辉瑞（BNT162b2）疫苗在保护个体免受感染方面的有效性超过 90%。然而，这些研究并未检测免疫功能低下的肾移植患者（KT）中的反应。随后在 KT 中的报告显示，Spike 特异性免疫球蛋白 G（IgG）反应严重缺乏，促使进行了加强接种，但对接种疫苗的 T 细胞免疫的更广泛了解尚不清楚。
我们检测了 61 例接受不同免疫抑制方案（ISP）（Tac+霉酚酸酯+泼尼松）与（贝利尤单抗+MMF+泼尼松）的 KT 患者和 41 例健康对照者的 SARS-CoV-2 Spike IgG 和 CD4+/CD8+Spike 特异性 T 细胞反应。我们还检测了两组中的巨细胞病毒-细胞毒性 T 细胞反应（CMV-Tc），以评估 T 细胞记忆。
我们的数据证实，两种 ISP（接种 BNT162b2 第二剂后，21%的患者表现出 Spike IgG 1M，而对照组为 93%）的接种疫苗的 KT 患者的 Spike IgG 反应较差。然而，35%的 Spike IgG（-）患者表现出 CD4+和/或 CD8+T 细胞反应。除了一名 CMV-IgG+患者外，所有患者均表现出良好的 CMV-Tc 反应。ISP 对 T 细胞免疫没有影响。
免疫功能低下的 KT 受者在接种疫苗后表现出严重的体液和 T 细胞免疫反应缺陷。接种疫苗后，ISP 对 KT 患者的 SARS-CoV-2 Spike 肽的免疫反应无差异。在缺乏 Spike IgG 的情况下检测到 Spike 特异性 T 细胞免疫表明，免疫功能低下的 KT 患者接种疫苗可能提供部分免疫，尽管不能预防感染，但 T 细胞免疫可能限制其严重程度。
