Ahn Bin, Kang Kyu Ri, Kim Ye Ji, Cho Yoon Kyung, Jo Suejung, Yoo Jae Won, Lee Jae Wook, Chung Nack-Gyun, Cho Bin, Jeong Dae Chul, Kang Jin Han, Kang Hyun Mi
Vaccine Bio Research Institute, College of Medicine, Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Pediatrics, College of Medicine, Catholic University of Korea, Seoul 06591, Republic of Korea.
Vaccines (Basel). 2024 Dec 5;12(12):1371. doi: 10.3390/vaccines12121371.
Varicella can lead to severe complications in immunocompromised children, including those undergoing hematopoietic stem cell transplantation (HSCT) or chemotherapy. Preventing primary varicella zoster virus (VZV) infection is crucial in these populations to mitigate morbidity and mortality. This study aimed to evaluate the immunogenicity and safety of the live attenuated MAV/06 varicella vaccine in pediatric patients post-HSCT and post-chemotherapy. Additionally, it sought to compare fluorescent-antibody-to-membrane-antigen (FAMA) and enzyme-linked immunosorbent assay (ELISA) titers to establish effective cut-off levels for protection against varicella.
The FAMA assay was conducted at the Vaccine Bio Research Institute, and a VARICELLA-ZOSTER ELISA (Vircell, Granada, Spain) kit, which relies on lysate from whole cells infected with VZV, was used to determine VZV IgG. A prospective cohort study was conducted with 76 pediatric patients under 18 years old who tested negative for VZV IgG via ELISA. Patients post-HSCT and post-chemotherapy were included. Participants received the MAV/06 varicella vaccine, and serologic responses were evaluated using ELISA and FAMA.
The median age of participants was 9.8 years, with acute lymphoid leukemia and acute myeloid leukemia being the most common underlying disease. Post-dose 1, the seropositive rate was 56.1% by ELISA and 97.2% by FAMA. Based on the FAMA seropositive cut-off ≥1:4, post-dose 1 geometric mean titers (GMTs) of seropositive patients in the post-HSCT group were 14.7 (95% CI, 11.3-19.1) versus 20.2 (95% CI, 13.0-31.3) in the post-chemotherapy group ( = 0.690). Based on a FAMA seropositive cut-off ≥1:16, the post-dose 1 GMT of patients considered seropositive in the post-HSCT group was 19.3 (95% CI, 15.6-24.0) versus 34.1 (95% CI, 21.0-55.4) in the post-chemotherapy group ( = 0.116), and post-dose 2 FAMA titers of 76.1 (95% CI, 14.6-398.1) in the post-HSCT group and 64.0 (95% CI, 11.4-358.1) in the post-HSCT group ( = 0.853) were observed. In patients with lower baseline FAMA titers (1:4 to 1:8), 66.7% in the post-HSCT group and 71.5% in the post-chemotherapy group achieved a greater than four-fold increase in FAMA titers post-dose 1, while those with higher baseline titers (≥1:16) did not. There were no serious adverse events or vaccine-related rashes occurring in any of the patients.
The MAV/06 varicella vaccine is immunogenic in pediatric patients post-HSCT and post-chemotherapy, particularly when administered in a two-dose schedule using a cut-off FAMA titer of <1:16.
水痘可导致免疫功能低下儿童出现严重并发症，包括接受造血干细胞移植（HSCT）或化疗的儿童。预防原发性水痘带状疱疹病毒（VZV）感染对这些人群减轻发病率和死亡率至关重要。本研究旨在评估减毒活MAV/06水痘疫苗在HSCT后和化疗后的儿科患者中的免疫原性和安全性。此外，它试图比较荧光抗体与膜抗原（FAMA）和酶联免疫吸附测定（ELISA）滴度，以确定预防水痘的有效临界值水平。
FAMA检测在疫苗生物研究所进行，使用一种依赖于感染VZV的全细胞裂解物的水痘带状疱疹ELISA（Vircell，西班牙格拉纳达）试剂盒来测定VZV IgG。对76名18岁以下通过ELISA检测VZV IgG呈阴性的儿科患者进行了一项前瞻性队列研究。纳入了HSCT后和化疗后的患者。参与者接种了MAV/06水痘疫苗，并使用ELISA和FAMA评估血清学反应。
参与者的中位年龄为9.8岁，最常见的基础疾病是急性淋巴细胞白血病和急性髓细胞白血病。接种第1剂后，ELISA检测的血清阳性率为56.1%，FAMA检测的血清阳性率为97.2%。基于FAMA血清阳性临界值≥1:4，HSCT后组血清阳性患者接种第1剂后的几何平均滴度（GMT）为14.7（95%CI，11.3 - 19.1），化疗后组为20.2（95%CI，13.0 - 31.3）（P = 0.690）。基于FAMA血清阳性临界值≥1:16，HSCT后组被认为血清阳性的患者接种第1剂后的GMT为19.3（95%CI，15.6 - 24.0），化疗后组为34.1（95%CI，21.0 - 55.4）（P = 0.116），观察到HSCT后组接种第2剂后的FAMA滴度为76.1（95%CI，14.6 - 398.1），化疗后组为64.0（95%CI，11.4 - 358.1）（P = 0.853）。在基线FAMA滴度较低（1:4至1:8）的患者中，HSCT后组66.7%和化疗后组71.5%的患者接种第1剂后FAMA滴度增加了四倍以上，而基线滴度较高（≥1:16）的患者则没有。所有患者均未发生严重不良事件或与疫苗相关的皮疹。
MAV/06水痘疫苗在HSCT后和化疗后的儿科患者中具有免疫原性，特别是在使用<1:16的FAMA滴度临界值进行两剂接种时。
