SARS-CoV-2mRNA全疫苗接种和加强剂量的体液和细胞反应以及尖峰变体的影响,包括Omicron,目前尚不清楚多发性骨髓瘤(MM)和癌前单克隆丙种球蛋白的患者。在这项研究中,涉及40名患者,我们发现,患有复发难治性疾病(MMR)的MM患者在接种SARS-CoV-2疫苗后,尖峰特异性抗体水平和中和滴度均降低.五个分析的变体,值得注意的是Omicron,对所有MM和闷烧MM患者中疫苗诱导的抗体的中和能力有显著的负面影响。此外,与具有未确定意义的单克隆丙种球蛋白病的患者相比,在MM患者中发现了较低的产生尖峰特异性IL-2的CD4T细胞和减少的产生细胞毒性尖峰特异性IFN-γ和TNF-α的CD8T细胞。我们发现,在新诊断的MM(MMD)患者和大多数患者中,异源加强免疫可改善SARS-CoV-2的体液和细胞反应,但不是全部,MMR患者。加强剂量后,在MMD中,针对几乎所有分析的变体的中和抗体滴度显著增加.然而,在MMR患者中,Omicron保留了对中和能力的负面影响,建议进一步加强SARS-CoV-2疫苗在这些患者中的有效性。
The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of the spike variants, including Omicron, are still unclear in patients with multiple myeloma (MM) and those with pre-malignant monoclonal gammopathies. In this study, involving 40 patients, we found that MM patients with relapsed-refractory disease (MMR) had reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 vaccination. The five analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and smoldering MM. Moreover, lower spike-specific IL-2-producing CD4+ T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing CD8+ T cells were found in MM patients as compared to patients with monoclonal gammopathy of undetermined significance. We found that a heterologous booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. However, in MMR patients, Omicron retained a negative impact on neutralizing ability, suggesting further approaches to potentiating the effectiveness of SARS-CoV-2 vaccination in these patients.