Department of Rheumatology, Erasmus Medical Center, Rotterdam, Netherlands
Medicines Evaluation Board, Utrecht, Netherlands.
RMD Open. 2023 Aug;9(3). doi: 10.1136/rmdopen-2023-002985.
While protection against pertussis following maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination was demonstrated in healthy term-born infants, no evidence is available on Tdap vaccination in combination with immune-modulating therapy during pregnancy. In this pilot study, we explored whether treatment with tumour necrosis factor alpha inhibitors (TNFis) in pregnant patients with rheumatic disease interferes with Tdap vaccine responses and affects maternal anti-pertussis IgG antibody levels in newborns.
Patients were included by a rheumatologist during pregnancy in case they received maternal Tdap vaccination in the late-second or early-third trimester of pregnancy. Blood samples were obtained from mothers during the first pregnancy trimester, 3 months after delivery and from the umbilical cord. IgG antibody levels against Tdap-included antigens were measured using a bead-based multiplex immunoassay. Findings on patients exposed to TNFis were compared with those from TNFi-unexposed patients and with data from a historical comparator study among healthy Tdap vaccinated mother-infant pairs (n=53).
66 patients (46 exposed and 20 unexposed to TNFIs) were enrolled. No major differences in IgG antibody levels were observed between TNFi-exposed and unexposed mothers before maternal Tdap vaccination and 3 months after delivery. In cord sera, however, antibody levels against pertussis toxin were significantly lower after TNFi-treatment (35.94 IU/mL, 95% CI 20.68 to 62.45) compared with no TNFi-treatment of mothers with rheumatic disease (94.61 IU/mL, 95% CI 48.89 to 183.07) and lower compared with a cohort of healthy mothers (125.12 IU/mL, 95% CI 90.75 to 172.50). We observed similar differences for filamentous haemagglutinin, pertactin, tetanus toxoid and diphtheria toxoid.
These preliminary data indicate no major differences in IgG antibody levels on maternal Tdap vaccination in pregnant women with or without immune-modulating treatment, although our findings suggest that TNFis during pregnancy induce lower maternal anti-pertussis-specific protective antibody levels in newborns.
虽然母体破伤风、白喉和无细胞百日咳(Tdap)疫苗接种可预防百日咳,但尚无证据表明妊娠期间联合使用免疫调节疗法进行 Tdap 疫苗接种的情况。在这项初步研究中,我们探讨了妊娠期间患有风湿性疾病的患者接受肿瘤坏死因子-α抑制剂(TNFis)治疗是否会干扰 Tdap 疫苗的反应,并影响新生儿母亲抗百日咳 IgG 抗体水平。
在妊娠期间,风湿病学家会纳入接受 Tdap 疫苗接种的母体患者。采集母亲在妊娠早期、产后 3 个月和脐带的血液样本。使用基于珠的多重免疫测定法测量针对 Tdap 包含抗原的 IgG 抗体水平。将暴露于 TNFis 的患者的发现与未暴露于 TNFis 的患者的发现以及来自健康 Tdap 疫苗接种的母婴对(n=53)的历史对照研究的数据进行比较。
纳入了 66 名患者(46 名暴露于 TNFis,20 名未暴露于 TNFis)。在母体 Tdap 疫苗接种前和产后 3 个月,暴露于 TNFis 的母亲与未暴露于 TNFis 的母亲的 IgG 抗体水平没有明显差异。然而,在脐带血清中,与未接受 TNFis 治疗的风湿性疾病母亲(94.61IU/mL,95%CI 48.89 至 183.07)相比,接受 TNFis 治疗的母亲的百日咳毒素抗体水平明显较低(35.94IU/mL,95%CI 20.68 至 62.45),与健康母亲队列相比(125.12IU/mL,95%CI 90.75 至 172.50)也较低。我们观察到对丝状血凝素、 pertactin、破伤风类毒素和白喉类毒素的类似差异。
这些初步数据表明,母体 Tdap 疫苗接种在接受或不接受免疫调节治疗的妊娠妇女中,IgG 抗体水平没有明显差异,尽管我们的发现表明妊娠期间 TNFis 会诱导新生儿母亲抗百日咳特异性保护性抗体水平降低。