Casetti Rita, Sacchi Alessandra, Mazzotta Valentina, Cristofanelli Flavia, Grassi Germana, Gili Simona, Cimini Eleonora, Notari Stefania, Bordoni Veronica, Mastrorosa Ilaria, Giancola Maria Letizia, Vergori Alessandra, Tempestilli Massimo, Vita Serena, Mariotti Davide, Rosati Silvia, Lalle Eleonora, Meschi Silvia, Colavita Francesca, Garbuglia Anna Rosa, Girardi Enrico, Nicastri Emanuele, Antinori Andrea, Agrati Chiara
Cellular Immunology and Pharmacology Laboratory, INMI L. Spallanzani, 00149 Rome, Italy.
Molecular Virology and Antimicrobic Immunity Laboratory, Department of Science, University of Rome Three, 00146 Rome, Italy.
Int Immunopharmacol. 2025 Feb 20;148:113934. doi: 10.1016/j.intimp.2024.113934. Epub 2025 Jan 19.
The impact of anti-Spike monoclonal antibody (mAbs) treatment on the immune response of COVID19-patients is poorly explored. In particular, a comparison of the immunological influence of different therapeutic regimens has not yet been performed. Aim of the study was to compare the kinetic of innate and adaptive immune response as well as the SARS-CoV-2 specific humoral and T cell response in two groups of SARS-CoV-2-infected patients treated with two different mAbs regimens: Bamlanivimab/Etesevimab (BAM/ETE) or Casirivimab/Imdevimab (CAS/IMD). SARS-CoV-2-infected patients (n = 39) with mild/moderate disease were enrolled before (T0) and after 7 days (T7) and 30 day (T30) from mAbs infusion. Patients were divided in two groups on the basis of the mAb regimen: BAM/ETE (n = 15) and CAS/IMD (n = 24). The phenotype/function of immune cell subsets was evaluated by flow-cytometry and by ELISA. The Spike-specific T cell response (IFN-γ) and anti-Nucleocapside IgG were evaluated by chemiluminescence assay. SARS CoV-2 RNA in nasal swabs was evaluated by RT-PCR. Eleven out of the thirty-nine enrolled patients tested negative at T7, among which nine (81.8 %) had been treated with CAS/IMD regimen. A comparable increase in CD4 and CD8 T cells was observed in both treatment groups. Moreover, a reduction of CD38 expression on T (CD4, CD8 and Vδ2) and on NK cells was observed in both groups, as well as a reduction overtime of the perforin expression in T (CD8, Vδ2) and in NK cells reaching significance only in CAS/IMD-treated patients. The SARS-CoV-2-specific T cells response increased at T7 in BAM/ETE-treated patients and at T30 in CAS/IND group. Of note, at T30 SARS-CoV2-specific T cells was higher in CAS/IMD than in BAM/ETE group. Furthermore, the titre of anti-N IgG increased overtime in both groups with a faster kinetic in CAS/IMD group. The spontaneous production of inflammatory cytokines by monocytes and neutrophils was similar the two mAb regimens, as well as the level of plasmatic IL-6. Finally, patients were also analysed according to sex. The male group showed a higher frequency of activated CD4 T cells, NKG2A-expressing CD8 T cells and perforin-expressing Vδ2 T cells compared to female group. Moreover, a higher specific T cell response at T30 was observed in the male compared to female group. In conclusion, these results show similar effects of both mAb regimens in restoring T and NK cell homeostasis and in reducing inflammation. In contrast, CAS/IMD allows a better humoral and cellular SARS-CoV2 specific immunization.
抗刺突单克隆抗体（mAbs）治疗对新冠患者免疫反应的影响尚未得到充分研究。特别是，尚未对不同治疗方案的免疫影响进行比较。本研究的目的是比较两组接受两种不同mAb方案治疗的新冠感染患者的固有免疫和适应性免疫反应动力学，以及新冠病毒2特异性体液和T细胞反应：巴瑞替尼/依替米星（BAM/ETE）或卡西瑞维单抗/英德维单抗（CAS/IMD）。在mAb输注前（T0）、输注后7天（T7）和30天（T30），招募了39例轻度/中度疾病的新冠感染患者。根据mAb方案将患者分为两组：BAM/ETE组（n = 15）和CAS/IMD组（n = 24）。通过流式细胞术和酶联免疫吸附测定法评估免疫细胞亚群的表型/功能。通过化学发光测定法评估刺突特异性T细胞反应（IFN-γ）和抗核衣壳IgG。通过逆转录-聚合酶链反应评估鼻拭子中的新冠病毒2 RNA。39例入组患者中有11例在T7时检测呈阴性，其中9例（81.8%）接受了CAS/IMD方案治疗。两个治疗组中均观察到CD4和CD8 T细胞有类似的增加。此外，两组中T（CD4、CD8和Vδ2）和NK细胞上CD38表达均降低，T（CD8、Vδ2）和NK细胞中穿孔素表达随时间降低，仅在接受CAS/IMD治疗的患者中达到显著水平。在接受BAM/ETE治疗的患者中，新冠病毒2特异性T细胞反应在T7时增加，在CAS/IND组中在T30时增加。值得注意的是，在T30时，CAS/IMD组的新冠病毒2特异性T细胞高于BAM/ETE组。此外，两组中抗N IgG滴度均随时间增加，CAS/IMD组的动力学更快。单核细胞和中性粒细胞自发产生炎性细胞因子的情况与两种mAb方案相似，血浆IL-6水平也相似。最后，还根据性别对患者进行了分析。与女性组相比，男性组中活化的CD4 T细胞、表达NKG2A的CD8 T细胞和表达穿孔素的Vδ2 T细胞的频率更高。此外，与女性组相比，男性组在T30时观察到更高的特异性T细胞反应。总之，这些结果表明两种mAb方案在恢复T和NK细胞稳态以及减轻炎症方面具有相似的效果。相比之下，CAS/IMD能实现更好的新冠病毒2特异性体液和细胞免疫。
