Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Campus Virchow, Augustenburger Platz 1/Südstraße 2, 13353, Berlin, Germany.
Berlin Institute of Health, Berlin, Germany.
J Clin Immunol. 2023 Jul;43(5):869-881. doi: 10.1007/s10875-023-01468-w. Epub 2023 Mar 17.
Humoral and cellular immune responses were described after COVID-19 vaccination in patients with common variable immunodeficiency disorder (CVID). This study aimed to investigate SARS-CoV-2-specific antibody quality and memory function of B cell immunity as well as T cell responses after COVID-19 vaccination in seroresponding and non-responding CVID patients.
We evaluated antibody avidity and applied a memory B cell ELSPOT assay for functional B cell recall memory response to SARS-CoV-2 after COVID-19 vaccination in CVID seroresponders. We comparatively analyzed SARS-CoV-2 spike reactive polyfunctional T cell response and reactive peripheral follicular T helper cells (pT) by flow cytometry in seroresponding and non-seroresponding CVID patients. All CVID patients had previously failed to mount a humoral response to pneumococcal conjugate vaccine.
SARS-CoV-2 spike antibody avidity of seroresponding CVID patients was significantly lower than in healthy controls. Only 30% of seroresponding CVID patients showed a minimal memory B cell recall response in ELISPOT assay. One hundred percent of CVID seroresponders and 83% of non-seroresponders had a detectable polyfunctional T cell response. Induction of antigen-specific CD4CD154CD137CXCR5 pT cells by the COVID-19 vaccine was higher in CVID seroresponder than in non-seroresponder. Levels of pT did not correlate with antibody response or avidity.
Reduced avidity and significantly impaired recall memory formation after COVID-19 vaccination in seroresponding CVID patients stress the importance of a more differentiated analysis of humoral immune response in CVID patients. Our observations challenge the clinical implications that follow the binary categorization into seroresponder and non-seroresponder.
描述了在普通变异性免疫缺陷病（CVID）患者中接种 COVID-19 疫苗后的体液和细胞免疫反应。本研究旨在调查 COVID-19 疫苗接种后血清反应性和非反应性 CVID 患者的 SARS-CoV-2 特异性抗体质量和 B 细胞免疫记忆功能以及 T 细胞反应。
我们评估了抗体亲和力，并在 COVID-19 疫苗接种后应用记忆 B 细胞 ELISPOT 测定法评估 SARS-CoV-2 的功能性 B 细胞回忆性记忆反应。我们通过流式细胞术比较分析了血清反应性和非血清反应性 CVID 患者中 SARS-CoV-2 刺突反应性多能性 T 细胞反应和反应性外周滤泡辅助 T 细胞（pT）。所有 CVID 患者先前均未能对肺炎球菌结合疫苗产生体液反应。
血清反应性 CVID 患者的 SARS-CoV-2 刺突抗体亲和力明显低于健康对照组。仅 30％的血清反应性 CVID 患者在 ELISPOT 测定中显示出最小的记忆 B 细胞回忆反应。100％的血清反应性 CVID 患者和 83％的非血清反应性患者均具有可检测的多能性 T 细胞反应。COVID-19 疫苗诱导的抗原特异性 CD4CD154CD137CXCR5 pT 细胞在血清反应性 CVID 患者中比非血清反应性患者更高。pT 水平与抗体反应或亲和力无关。
血清反应性 CVID 患者接种 COVID-19 疫苗后亲和力降低且明显记忆形成受损，强调了对 CVID 患者体液免疫反应进行更差异化分析的重要性。我们的观察结果挑战了根据血清反应性和非血清反应性进行二元分类的临床意义。
