Speth Fabian, Hinze Claas H, Andel Susanne, Mertens Thomas, Haas Johannes-Peter
German Center for Pediatric and Adolescent Rheumatology, Gehfeldstr. 24, 82467, Garmisch-Partenkirchen, Germany.
Department of Pediatric Rheumatology and Immunology, University Hospital Münster, Albert-Schweitzer-Campus I, Building W30, 48149, Münster, Germany.
Pediatr Rheumatol Online J. 2018 Mar 2;16(1):15. doi: 10.1186/s12969-018-0231-3.
The goal of this study was to apply the varicella zoster virus (VZV) vaccine to patients with pediatric rheumatic diseases (PRD) at risk for severe chickenpox, without interrupting their current immunosuppression, including biological agents, using an immunological-based pre-vaccination checklist to assure safety. A pre-vaccination checklist was implemented to ensure adequate immune competence prior to immunization.
This prospective study included seronegative patients (VZV-IgG ≤200 mIU/ml) and patients who had previously received only a single dose of VZV vaccine. All vaccinees demonstrated clinically inactive PRD. Patients were categorized according to their actual treatment in low-intensity IS (LIIS) and high-intensity IS (HIIS) including biological therapy. The pre-vaccination checklist defined thresholds for the following basic laboratory tests: white blood cell count ≥3000/mm, lymphocytes ≥1200/mm, serum IgG ≥500 mg/dl, IgM ≥20 mg/dl, tetanus toxoid antibody ≥0.1 IU/ml. In case of HIIS additional specifications included a CD4+ lymphocyte count ≥200/mm and a positive T-cell function (via analyzable positive control of a standard tuberculosis interferon-gamma-release-assay (TB-IGRA) indicating mitogen-induced T cell proliferation). Patients who met the criteria of the pre-vaccination checklist received the first and/or second VZV vaccination. Immunologic response and side effects were monitored.
Twenty-three patients were recruited of whom nine had already received one VZV immunization before initiating IS. All patients met the pre-vaccination checklist criteria despite ongoing IS. There was no overall difference in VZV-IgG levels when comparing the LIIS (n=9) and HIIS (n=14) groups. In total, 21 patients (91%) showed a positive vaccination response, after the first immunization the median VZV-IgG across all patients was 224 (59-1219) mIU/ml (median (range)), after booster immunization it increased to 882 (30-4685) mIU/ml. Two patients in the HIIS group failed to raise positive VZV-IgG, despite booster immunization. All nine patients receiving only the second immunization on IS reached high titers of VZV-IgG >500 mIU/ml (1117 (513-4685) mIU/ml). There were no cases of rash or other vaccine-induced varicella disease symptoms and no evidence of PRD flare.
VZV vaccination is safe and largely immunogenic in children with ongoing IS fulfilling an immunological based pre-vaccination checklist. This new approach is based on immunologic function rather than on type of medications.
ISRCRTN trial registration number 21654693 , date of registration February 12, 2018, retrospectively registered.
本研究的目的是将水痘带状疱疹病毒（VZV）疫苗应用于有严重水痘风险的小儿风湿性疾病（PRD）患者，且不中断他们当前的免疫抑制治疗，包括生物制剂，通过基于免疫的接种前检查表来确保安全。实施接种前检查表以确保免疫接种前有足够的免疫能力。
这项前瞻性研究纳入了血清阴性患者（VZV-IgG≤200 mIU/ml）和之前仅接种过一剂VZV疫苗的患者。所有接种疫苗者的PRD临床症状均未发作。根据患者实际接受的低强度免疫抑制（LIIS）和高强度免疫抑制（HIIS）治疗（包括生物治疗）进行分类。接种前检查表定义了以下基本实验室检查的阈值：白细胞计数≥3000/mm³，淋巴细胞≥1200/mm³，血清IgG≥500 mg/dl，IgM≥20 mg/dl，破伤风类毒素抗体≥0.1 IU/ml。对于HIIS，额外的标准包括CD4⁺淋巴细胞计数≥200/mm³和阳性T细胞功能（通过标准结核干扰素-γ释放试验（TB-IGRA）的可分析阳性对照表明有丝分裂原诱导的T细胞增殖）。符合接种前检查表标准的患者接受第一剂和/或第二剂VZV疫苗接种。监测免疫反应和副作用。
招募了23名患者，其中9名在开始免疫抑制治疗前已接种过一剂VZV疫苗。尽管正在进行免疫抑制治疗，但所有患者均符合接种前检查表标准。比较LIIS组（n = 9）和HIIS组（n = 14）时，VZV-IgG水平无总体差异。总共有21名患者（91%）显示接种反应呈阳性，首次免疫后所有患者的VZV-IgG中位数为224（59 - 1219）mIU/ml（中位数（范围）），加强免疫后升至882（30 - 4685）mIU/ml。HIIS组有两名患者尽管进行了加强免疫，但VZV-IgG未升高至阳性。所有9名仅在免疫抑制治疗期间接受第二次免疫接种的患者VZV-IgG均达到>500 mIU/ml的高滴度（1117（513 - 4685）mIU/ml）。没有皮疹或其他疫苗诱导的水痘疾病症状的病例，也没有PRD病情加重的证据。
对于正在接受免疫抑制治疗且符合基于免疫的接种前检查表的儿童，VZV疫苗接种是安全的，且在很大程度上具有免疫原性。这种新方法基于免疫功能而非药物类型。
ISRCRTN试验注册号21654693，注册日期2018年2月12日，追溯注册。
