Pediatric Hematology and Stem Cell Transplantation Department, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary.
Department of Special Immunization Services, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary.
Front Immunol. 2022 Jun 17;13:907125. doi: 10.3389/fimmu.2022.907125. eCollection 2022.
Common variable immunodeficiency (CVID) patients have markedly decreased immune response to vaccinations. In this study we evaluated humoral and T cell-mediated responses against severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) with additional flow cytometric changes in CVID patients receiving booster vaccination with BNT162b2 after two ChAdOx1 nCoV-19. The BNT162b2 vaccine raised the anti-spike protein S immunoglobulin G over the cut-off value from 70% to 83% in CVID, anti-neutralizing antibody had been raised over a cut-off value from 70% to 80% but levels after boosting were significantly less in both tests than in healthy controls (*p=0.02; **p=0.009 respectively). Anti-SARS-CoV-2 immunoglobulin A became less positive in CVID after boosting, but the difference was not significant. The cumulative interferon-γ positive T cell response by ELISpot was over the cut-off value in 53% of the tested individuals and raised to 83% after boosting. This and flow cytometric control of cumulative CD4+ and CD8+ virus-specific T cell absolute counts in CVID were also statistically not different from healthy individuals after boosting. Additional flow cytometric measures for CD45+ lymphocytes, CD3+, and CD19+ cells have not shown significant differences from controls except for lower CD4+T cell counts at both time points (**p=0.003; **p=0.002), in parallel CD4+ virus-specific T-cell ratio was significantly lower in CVID patients at the first time point (*p: 0.03). After boosting, in more than 33% of both CVID patients and also in their healthy controls we detected a decrease in absolute CD45+, CD3+, CD3+CD4+, and CD3+CD8+, CD19+, and CD16+56+ cell counts. CD16+CD56+ cell counts were significantly lower compared to controls before and after boosting (*p=0.02, *p=0.02). CVID patients receiving immunosuppressive therapy throughout the previous year or autologous stem cell transplantation two years before vaccination had worse responses in anti-spike, anti-neutralizing antibody, CD3+CD4+T, CD19+ B, and natural killer cell counts than the whole CVID group. Vaccinations had few side effects. Based on these data, CVID patients receiving booster vaccination with BNT162b2 after two ChadOx1 can effectively elevate the levels of protection against COVID-19 infection, but the duration of the immune response together with COVID-19 morbidity data needs further investigation among these patients.
常见变异性免疫缺陷（CVID）患者对疫苗的免疫反应明显下降。在这项研究中，我们评估了 CVID 患者在接种两剂 ChAdOx1 nCoV-19 后接受 BNT162b2 加强免疫时对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的体液和 T 细胞介导的反应，并进行了额外的流式细胞术检测。BNT162b2 疫苗使 CVID 患者的抗刺突蛋白 S 免疫球蛋白 G 超过了 70%的临界值，达到了 83%；抗中和抗体也超过了 70%的临界值，达到了 80%，但加强免疫后的水平在两项检测中均显著低于健康对照组（*p=0.02；**p=0.009）。在加强免疫后，CVID 患者的抗 SARS-CoV-2 免疫球蛋白 A 呈阳性的比例降低，但差异无统计学意义。ELISpot 累积干扰素-γ阳性 T 细胞反应的阳性率在 53%的受检者中超过了临界值，加强免疫后提高到了 83%。在加强免疫后，CVID 患者的累积 CD4+和 CD8+病毒特异性 T 细胞绝对计数的流式细胞术控制也与健康个体无统计学差异。除了在两个时间点的 CD4+T 细胞计数较低（**p=0.003；**p=0.002）外，额外的流式细胞术测量 CD45+淋巴细胞、CD3+和 CD19+细胞均与对照组无显著差异，并且在 CVID 患者中，第一时间点的 CD4+病毒特异性 T 细胞比值显著较低（*p：0.03）。在加强免疫后，CVID 患者和其健康对照组中，超过 33%的患者出现了绝对 CD45+、CD3+、CD3+CD4+、CD3+CD8+、CD19+和 CD16+56+细胞计数的下降。与加强免疫前后的对照组相比，CD16+CD56+细胞计数明显降低（*p=0.02，*p=0.02）。在过去一年中接受免疫抑制治疗或在接种疫苗前两年接受自体干细胞移植的 CVID 患者，其抗刺突、抗中和抗体、CD3+CD4+T、CD19+B 和自然杀伤细胞计数的反应均较整个 CVID 组差。疫苗接种的副作用较少。基于这些数据，在接种两剂 ChAdOx1 nCoV-19 后接受 BNT162b2 加强免疫的 CVID 患者可以有效地提高对 COVID-19 感染的保护水平，但需要进一步研究这些患者的免疫反应持续时间和 COVID-19 发病率数据。
