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接种白喉破伤风疫苗以激活实体瘤患儿的适应性免疫

Vaccination Against Diphtheria and Tetanus as a Way to Activate Adaptive Immunity in Children with Solid Tumors.

机构信息

Department of Allergology, I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia.

Department of Epidemiology and Modern Vaccination Technologies, Sechenov First Moscow State Medical University, Moscow, Russia.

出版信息

Front Immunol. 2021 Jul 8;12:696816. doi: 10.3389/fimmu.2021.696816. eCollection 2021.

Abstract

Early studies on vaccination of children with oncological diseases were only dedicated to the assessment of safety and immunogenicity of the drug. Mechanisms of the post-vaccination immune response were not investigated. This study involved 41 patients aged 7-15 years who were treated for solid tumors two or more years ago. Of these, 26 were vaccinated against diphtheria and tetanus with ADS-m toxoid. Fifteen children (i.e., controls) were not vaccinated. The vaccination tolerability and clinical characteristics of the underlying disease remission ware assessed. Lymphocyte subpopulations were investigated over time by flow cytometry at 1, 6, and 12 months. IgG anti-diphtheria and anti-tetanus toxoids levels were assessed by ELISA. Within the first day of the post-vaccination period, two (7.7%) children demonstrated moderate local reactions and increased body temperature (up to 38.0°C). Relapse and metastasis were not mentioned within a year after immunization. An increase in concentration of IgG antibodies, maintained for 12 months, were noted [2.1 (1.3-3.4) IU/ml against diphtheria (p <0.001), 6.4 (2.3-9.7) IU/ml against tetanus (p <0.001)]. In contrast to healthy children, those with a history of cancer demonstrated a decrease in the relative number of mature T lymphocytes, as well as in absolute number of cytotoxic T cells and B lymphocytes. In a month after the revaccination, a significant increase in absolute (p = 0.04) and relative (p = 0.007) numbers of T lymphocytes and T helpers was revealed. In a year, these values decreased to baseline levels. As for helpers, they decreased below baseline and control values (p = 0.004). In a year after the vaccination, there was a significant (p = 0.05) increase in lymphocyte level with a decrease in the number of NK cells and B cells as compared with controls. Revaccination against diphtheria and tetanus promoted proliferation of a total lymphocytic cell pool along with restoration of the T lymphocyte subpopulation in children with a history of solid tumors. The ADS-m toxoid has a certain nonspecific immunomodulatory effect. These findings are important, also in the midst of the coronavirus pandemic.

摘要

早期针对患有肿瘤疾病的儿童进行疫苗接种的研究仅致力于评估药物的安全性和免疫原性。疫苗接种后的免疫反应机制并未得到研究。本研究纳入了 41 名年龄在 7-15 岁之间的患者,他们在两年前接受了实体瘤治疗。其中 26 名患者接种了 ADS-m 类毒素白喉和破伤风疫苗。15 名儿童(即对照组)未接种疫苗。评估了疫苗接种的耐受性和基础疾病缓解的临床特征。通过流式细胞术在接种后 1、6 和 12 个月对淋巴细胞亚群进行了随时间的研究。通过 ELISA 评估 IgG 抗白喉和破伤风类毒素水平。在接种后的第一天,有两名(7.7%)儿童出现中度局部反应和体温升高(高达 38.0°C)。免疫接种后一年内未提及复发和转移。接种后 12 个月内 IgG 抗体浓度增加[白喉 2.1(1.3-3.4)IU/ml(p<0.001),破伤风 6.4(2.3-9.7)IU/ml(p<0.001)]。与健康儿童相比,患有癌症的儿童成熟 T 淋巴细胞的相对数量以及细胞毒性 T 细胞和 B 淋巴细胞的绝对数量减少。在复种后的一个月,发现绝对(p=0.04)和相对(p=0.007)数量的 T 淋巴细胞和 T 辅助细胞均显著增加。一年后,这些值降至基线水平。至于辅助细胞,它们降至低于基线和对照组水平(p=0.004)。在接种疫苗一年后,与对照组相比,NK 细胞和 B 细胞数量减少,淋巴细胞水平显著升高(p=0.05)。白喉和破伤风复种可促进总淋巴细胞池的增殖,并恢复患有实体瘤儿童的 T 淋巴细胞亚群。 ADS-m 类毒素具有一定的非特异性免疫调节作用。这些发现很重要,即使在冠状病毒大流行期间也是如此。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac3c/8296462/ee5568660e3b/fimmu-12-696816-g001.jpg

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