Szabó Enikő, Modok Szabolcs, Rónaszéki Benedek, Faragó Anna, Gémes Nikolett, Nagy Lajos I, Hackler László, Farkas Katalin, Neuperger Patrícia, Balog József Á, Balog Attila, Puskás László G, Szebeni Gabor J
Laboratory of Functional Genomics, Biological Research Centre, Szeged, Hungary.
Department of Medicine, Szent-Györgyi Albert Medical School-University of Szeged, Szeged, Hungary.
Front Med (Lausanne). 2023 Jul 17;10:1176168. doi: 10.3389/fmed.2023.1176168. eCollection 2023.
Vaccination has proven the potential to control the COVID-19 pandemic worldwide. Although recent evidence suggests a poor humoral response against SARS-CoV-2 in vaccinated hematological disease (HD) patients, data on vaccination in these patients is limited with the comparison of mRNA-based, vector-based or inactivated virus-based vaccines.
Forty-nine HD patients and 46 healthy controls (HCs) were enrolled who received two-doses complete vaccination with BNT162b2, or AZD1222, or BBIBP-CorV, respectively. The antibodies reactive to the receptor binding domain of spike protein of SARS-CoV-2 were assayed by Siemens ADVIA Centaur assay. The reactive cellular immunity was assayed by flow cytometry. The PBMCs were reactivated with SARS-CoV-2 antigens and the production of activation-induced markers (TNF-α, IFN-γ, CD40L) was measured in CD4 or CD8 T-cells .
The anti-RBD IgG level was the highest upon BNT162b2 vaccination in HDs (1264 BAU/mL) vs. HCs (1325 BAU/mL) among the studied groups. The BBIBP-CorV vaccination in HDs (339.8 BAU/mL < 0.001) and AZD1222 in HDs (669.9 BAU/mL * < 0.05) resulted in weaker antibody response vs. BNT162b2 in HCs. The response rate of IgG production of HC vs. HD patients above the diagnostic cut-off value was 100% vs. 72% for the mRNA-based BNT162b2 vaccine; 93% vs. 56% for the vector-based AZD1222, or 69% vs. 33% for the inactivated vaccine BBIBP-CorV, respectively. Cases that underwent the anti-CD20 therapy resulted in significantly weaker ( < 0.01) anti-RBD IgG level (302 BAU/mL) than without CD20 blocking in the HD group (928 BAU/mL). The response rates of CD4 TNF-α, CD4 IFN-γ, or CD4 CD40L cases were lower in HDs vs. HCs in all vaccine groups. However, the BBIBP-CorV vaccine resulted the highest CD4 TNF-α and CD4 IFN-γ T-cell mediated immunity in the HD group.
We have demonstrated a significant weaker overall response to vaccines in the immunologically impaired HD population vs. HCs regardless of vaccine type. Although, the humoral immune activity against SARS-CoV-2 can be highly evoked by mRNA-based BNT162b2 vaccination compared to vector-based AZD1222 vaccine, or inactivated virus vaccine BBIBP-CorV, whereas the CD4 T-cell mediated cellular activity was highest in HDs vaccinated with BBIBP-CorV.
疫苗接种已证明在全球范围内控制新冠疫情具有潜力。尽管近期证据表明，接种疫苗的血液系统疾病（HD）患者对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的体液免疫反应较差，但与基于信使核糖核酸（mRNA）、基于载体或基于灭活病毒的疫苗相比，这些患者的疫苗接种数据有限。
招募了49例HD患者和46例健康对照（HC），他们分别接受了两剂BNT162b2、或AZD1222、或BBIBP-CorV的全程疫苗接种。采用西门子ADVIA Centaur检测法检测对SARS-CoV-2刺突蛋白受体结合域有反应的抗体。通过流式细胞术检测反应性细胞免疫。用SARS-CoV-2抗原重新激活外周血单个核细胞（PBMC），并在CD4或CD8 T细胞中测量激活诱导标志物（肿瘤坏死因子-α、干扰素-γ、CD40L）的产生。
在研究组中，HD患者接种BNT162b2疫苗后的抗受体结合域（RBD）免疫球蛋白G（IgG）水平最高（1264 BAU/mL），高于HC（1325 BAU/mL）。HD患者接种BBIBP-CorV疫苗（339.8 BAU/mL，P<0.001）和AZD1222疫苗（669.9 BAU/mL，P<0.05）后的抗体反应比HC患者接种BNT162b2疫苗后的反应弱。基于mRNA的BNT162b2疫苗，HC患者与HD患者IgG产生高于诊断临界值的反应率分别为100%和72%；基于载体的AZD1222疫苗分别为93%和56%；灭活疫苗BBIBP-CorV分别为69%和33%。在HD组中，接受抗CD20治疗的病例的抗RBD IgG水平（302 BAU/mL）显著低于未进行CD20阻断的病例（928 BAU/mL）（P<0.01）。在所有疫苗组中，HD患者的CD4肿瘤坏死因子-α、CD4干扰素-γ或CD4 CD40L病例的反应率均低于HC患者。然而，BBIBP-CorV疫苗在HD组中产生的CD4肿瘤坏死因子-α和CD4干扰素-γ T细胞介导的免疫最高。
我们已经证明，无论疫苗类型如何，免疫功能受损的HD人群对疫苗的总体反应明显弱于HC人群。尽管与基于载体的AZD1222疫苗或灭活病毒疫苗BBIBP-CorV相比，基于mRNA的BNT162b2疫苗能高度激发针对SARS-CoV-2的体液免疫活性，但接种BBIBP-CorV疫苗的HD患者中，CD4 T细胞介导的细胞活性最高。
