PDF(Pubmed)
Abstract：
Individuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.
In a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.
263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.
Immunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.
EudraCT Number: 2021-000291-11.
In a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.
263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.
Immunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.
EudraCT Number: 2021-000291-11.
摘要：
继发性免疫缺陷的个体属于最容易屈服于COVID-19的群体，因此优先考虑接种SARS-CoV-2疫苗。然而,在这些患者中,关于SARS-CoV-2-mRNA疫苗接种后的持续性和记忆记忆反应的知识有限.
在未来，开放标签，四期试验我们分析了S1特异性IgG，先前未感染的癌症或自身免疫性疾病患者在初次mRNA疫苗接种期间和加强后长达一个月的中和抗体和细胞因子反应。
263例实体瘤患者（SOT，n=63),多发性骨髓瘤（MM，n=70),炎症性肠病(IBD，n=130）和66个对照进行了分析。在两剂量初次疫苗接种后一个月，最高的无应答率与较低的CD19B细胞计数相关，并且在MM患者中发现（17％）。在对照组和IBD患者中，S1特异性IgG水平与IL-2和IFN-γ反应相关，但不是在癌症患者身上。第二次给药六个月后，18%的MM患者，SOT的10％和IBD的4％成为血清阴性；对照组中没有人成为阴性。然而,在用TNF-α抑制剂治疗的IBD患者中，抗体水平比对照组下降得更快.总的来说,用mRNA-1273接种导致比BNT162b2更高的抗体水平。重要的是,在血清反应者中,加强疫苗接种可使抗体水平增加>8倍,即使在无法检测到加强前抗体水平的患者中,也可诱导记忆记忆反应.然而，即使在加强疫苗接种后，使用TNF-α抑制剂的IBD患者中，抗体水平低于未治疗IBD患者和对照组.
疫苗特异性抗体和细胞反应的免疫监测似乎有助于确定疫苗接种失败，从而建立个性化的疫苗接种时间表。包括较短的助推器间隔，并有助于提高所有继发性免疫缺陷患者的疫苗效力。
EudraCT编号：2021-000291-11。
在未来，开放标签，四期试验我们分析了S1特异性IgG，先前未感染的癌症或自身免疫性疾病患者在初次mRNA疫苗接种期间和加强后长达一个月的中和抗体和细胞因子反应。
263例实体瘤患者（SOT，n=63),多发性骨髓瘤（MM，n=70),炎症性肠病(IBD，n=130）和66个对照进行了分析。在两剂量初次疫苗接种后一个月，最高的无应答率与较低的CD19B细胞计数相关，并且在MM患者中发现（17％）。在对照组和IBD患者中，S1特异性IgG水平与IL-2和IFN-γ反应相关，但不是在癌症患者身上。第二次给药六个月后，18%的MM患者，SOT的10％和IBD的4％成为血清阴性；对照组中没有人成为阴性。然而,在用TNF-α抑制剂治疗的IBD患者中，抗体水平比对照组下降得更快.总的来说,用mRNA-1273接种导致比BNT162b2更高的抗体水平。重要的是,在血清反应者中,加强疫苗接种可使抗体水平增加>8倍,即使在无法检测到加强前抗体水平的患者中,也可诱导记忆记忆反应.然而，即使在加强疫苗接种后，使用TNF-α抑制剂的IBD患者中，抗体水平低于未治疗IBD患者和对照组.
疫苗特异性抗体和细胞反应的免疫监测似乎有助于确定疫苗接种失败，从而建立个性化的疫苗接种时间表。包括较短的助推器间隔，并有助于提高所有继发性免疫缺陷患者的疫苗效力。
EudraCT编号：2021-000291-11。
