PDF(Pubmed)
Abstract：
Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective long-term protection against COVID-19 is therefore of great importance in these patients, but little is known about the decay of the immune response after primary vaccination. We studied the immune responses 6 months after two mRNA-1273 COVID-19 vaccines in 473 IEI patients and subsequently the response to a third mRNA COVID-19 vaccine in 50 patients with common variable immunodeficiency (CVID).
In a prospective multicenter study, 473 IEI patients (including X-linked agammaglobulinemia (XLA) (N = 18), combined immunodeficiency (CID) (N = 22), CVID (N = 203), isolated or undefined antibody deficiencies (N = 204), and phagocyte defects (N = 16)), and 179 controls were included and followed up to 6 months after two doses of the mRNA-1273 COVID-19 vaccine. Additionally, samples were collected from 50 CVID patients who received a third vaccine 6 months after primary vaccination through the national vaccination program. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T cell responses were assessed.
At 6 months after vaccination, the geometric mean antibody titers (GMT) declined in both IEI patients and healthy controls, when compared to GMT 28 days after vaccination. The trajectory of this decline did not differ between controls and most IEI cohorts; however, antibody titers in CID, CVID, and isolated antibody deficiency patients more often dropped to below the responder cut-off compared to controls. Specific T cell responses were still detectable in 77% of controls and 68% of IEI patients at 6 months post vaccination. A third mRNA vaccine resulted in an antibody response in only two out of 30 CVID patients that did not seroconvert after two mRNA vaccines.
A similar decline in IgG titers and T cell responses was observed in patients with IEI when compared to healthy controls 6 months after mRNA-1273 COVID-19 vaccination. The limited beneficial benefit of a third mRNA COVID-19 vaccine in previous non-responder CVID patients implicates that other protective strategies are needed for these vulnerable patients.
In a prospective multicenter study, 473 IEI patients (including X-linked agammaglobulinemia (XLA) (N = 18), combined immunodeficiency (CID) (N = 22), CVID (N = 203), isolated or undefined antibody deficiencies (N = 204), and phagocyte defects (N = 16)), and 179 controls were included and followed up to 6 months after two doses of the mRNA-1273 COVID-19 vaccine. Additionally, samples were collected from 50 CVID patients who received a third vaccine 6 months after primary vaccination through the national vaccination program. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T cell responses were assessed.
At 6 months after vaccination, the geometric mean antibody titers (GMT) declined in both IEI patients and healthy controls, when compared to GMT 28 days after vaccination. The trajectory of this decline did not differ between controls and most IEI cohorts; however, antibody titers in CID, CVID, and isolated antibody deficiency patients more often dropped to below the responder cut-off compared to controls. Specific T cell responses were still detectable in 77% of controls and 68% of IEI patients at 6 months post vaccination. A third mRNA vaccine resulted in an antibody response in only two out of 30 CVID patients that did not seroconvert after two mRNA vaccines.
A similar decline in IgG titers and T cell responses was observed in patients with IEI when compared to healthy controls 6 months after mRNA-1273 COVID-19 vaccination. The limited beneficial benefit of a third mRNA COVID-19 vaccine in previous non-responder CVID patients implicates that other protective strategies are needed for these vulnerable patients.
摘要：
目标：先天性免疫错误（IEI）患者患严重冠状病毒病-2019（COVID-19）的风险增加。因此，有效的长期预防COVID-19对这些患者非常重要，但是对初次接种疫苗后免疫反应的衰减知之甚少。我们研究了473例IEI患者的两种mRNA-1273COVID-19疫苗接种后6个月的免疫反应，随后研究了50例常见可变免疫缺陷（CVID）患者对第三种mRNACOVID-19疫苗的反应。
方法：在一项前瞻性多中心研究中，473例IEI患者（包括X连锁无丙种球蛋白血症（XLA）（N=18），联合免疫缺陷（CID）（N=22），CVID（N=203），孤立或未定义的抗体缺陷（N=204），和吞噬细胞缺陷（N=16）），179名对照纳入研究，并在两剂mRNA-1273COVID-19疫苗接种后随访6个月。此外,我们收集了50例CVID患者的样本,这些患者在通过国家疫苗接种计划进行初次疫苗接种后6个月接受了第三次疫苗接种.SARS-CoV-2特异性IgG滴度,中和抗体，评估T细胞反应。
结果：接种后6个月，IEI患者和健康对照的几何平均抗体滴度（GMT）均下降，与疫苗接种后28天的GMT相比。这种下降的轨迹在对照组和大多数IEI队列之间没有差异；然而，CID中的抗体滴度，CVID,与对照组相比，分离的抗体缺乏症患者更经常下降到低于反应者的临界值。在接种后6个月,在77%的对照和68%的IEI患者中仍可检测到特异性T细胞应答。第三种mRNA疫苗在30名CVID患者中仅有两名在两种mRNA疫苗后没有血清转化的患者中产生抗体应答。
结论：在接种mRNA-1273COVID-19后6个月，与健康对照组相比，IEI患者的IgG滴度和T细胞反应下降相似。第三种mRNACOVID-19疫苗对先前无反应的CVID患者的有益益处有限，这表明这些脆弱的患者需要其他保护策略。
方法：在一项前瞻性多中心研究中，473例IEI患者（包括X连锁无丙种球蛋白血症（XLA）（N=18），联合免疫缺陷（CID）（N=22），CVID（N=203），孤立或未定义的抗体缺陷（N=204），和吞噬细胞缺陷（N=16）），179名对照纳入研究，并在两剂mRNA-1273COVID-19疫苗接种后随访6个月。此外,我们收集了50例CVID患者的样本,这些患者在通过国家疫苗接种计划进行初次疫苗接种后6个月接受了第三次疫苗接种.SARS-CoV-2特异性IgG滴度,中和抗体，评估T细胞反应。
结果：接种后6个月，IEI患者和健康对照的几何平均抗体滴度（GMT）均下降，与疫苗接种后28天的GMT相比。这种下降的轨迹在对照组和大多数IEI队列之间没有差异；然而，CID中的抗体滴度，CVID,与对照组相比，分离的抗体缺乏症患者更经常下降到低于反应者的临界值。在接种后6个月,在77%的对照和68%的IEI患者中仍可检测到特异性T细胞应答。第三种mRNA疫苗在30名CVID患者中仅有两名在两种mRNA疫苗后没有血清转化的患者中产生抗体应答。
结论：在接种mRNA-1273COVID-19后6个月，与健康对照组相比，IEI患者的IgG滴度和T细胞反应下降相似。第三种mRNACOVID-19疫苗对先前无反应的CVID患者的有益益处有限，这表明这些脆弱的患者需要其他保护策略。
