Sabino-Santos Gilberto, Leggio Cathryn E, Litwin Sean M, Waheed Najia, Bai Shuangyi, Ulusan Sinem, Karunathilake Anoli, Elliott Debra H, Smira Ashley R, Chandra Sruti, Li Lin, Ning Bo, Hu Tony, Schieffelin John S, Gunn Bronwyn M, Robinson James E, Fuloria Jyotsna, Norton Elizabeth B
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
University Medical Center New Orleans, New Orleans, Louisiana, USA.
Immun Inflamm Dis. 2024 Dec;12(12):e70039. doi: 10.1002/iid3.70039.
SARS-CoV-2 monoclonal antibody (mAB) therapy has effectively treated severe COVID-19, although how this contributes to protective antiviral immunity in settings of malignancy is poorly defined.
We evaluated the development of post-infection immunity in five patients with malignancies who received mAB therapy targeting spike protein for their PCR-confirmed SARS-CoV-2 infection in 2021, compared with non-mAB controls. Patients were identified from a larger study on oncology with a history or documented current infection with SARS-CoV-2. Subjects include two patients with lymphoma and CD20-depletion therapy, one with myeloma and two with solid tumor (stage IIA rectal adenocarcinoma and metastatic breast cancer). Cancer therapies and COVID vaccination history varied by patient. Blood samples (1-4 per patient) were collected 71-635 days post-mAB therapy. We employed clinical histories with comprehensive immunoprofiling analysis, including systems serology antibody isotyping and effector function, T-cell immunophenotyping for subset and memory cells, and sensitive blood viral RNA detection up to 2 years post-mAB therapy.
B-cell deficiency was confirmed in 3/5 patients. All patients had detectable anti-spike and nucleoprotein antibody isotypes, effector functions, and neutralizing antibodies (which increased over time by subject) at similar levels to the control group. Virus-specific T-cell activation and phenotypes varied by time and patient. Spike-specific effector and memory CD8 + T-cells were significantly elevated in mAB subjects compared to the control group. SARS-CoV-2 viral RNA detection was also higher in mAB-treated patients. One patient on bortezomib therapy had unique alterations in these populations.
All mAB-treated patients with malignancies developed polyfunctional immunity humoral and T-cell immunity to SARS-CoV-2 even in the setting of B-cell deficiency. The evolution of this immunity, including new variant-specific antibodies, without secondary illnesses suggests that patients were protected from symptomatic re-infection, and mAB therapy did not blunt the development of host immunity. Future studies are warranted to better characterize immunologic memory over time with exposures to new viral variants, evaluate prolonged viral shedding and the continued use of appropriate mAB for infection in high-risk patients.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）单克隆抗体（mAB）疗法已有效治疗了重症2019冠状病毒病（COVID-19），尽管其在恶性肿瘤患者中如何促进保护性抗病毒免疫的作用尚不明确。
我们评估了5例接受针对刺突蛋白的mAB疗法治疗其2021年经聚合酶链反应（PCR）确诊的SARS-CoV-2感染的恶性肿瘤患者感染后免疫的发展情况，并与未接受mAB治疗的对照组进行比较。这些患者是从一项更大规模的肿瘤学研究中识别出来的，他们有SARS-CoV-2感染史或当前感染的记录。受试者包括2例接受CD20清除疗法的淋巴瘤患者、1例骨髓瘤患者和2例实体瘤患者（IIA期直肠腺癌和转移性乳腺癌）。不同患者的癌症治疗方法和COVID疫苗接种史各不相同。在mAB治疗后71至635天采集血样（每位患者1至4份）。我们采用临床病史并结合全面的免疫分析，包括系统血清学抗体亚型分析和效应功能分析、T细胞免疫表型分析以确定亚群和记忆细胞，以及在mAB治疗后长达2年的时间里进行敏感的血液病毒RNA检测。
5例患者中有3例确诊存在B细胞缺陷。所有患者均可检测到抗刺突蛋白和核蛋白抗体亚型、效应功能及中和抗体（随时间推移各受试者的中和抗体水平均有所升高），其水平与对照组相似。病毒特异性T细胞的激活情况和表型因时间和患者而异。与对照组相比，接受mAB治疗的患者中刺突蛋白特异性效应和记忆性CD8+T细胞显著升高。接受mAB治疗的患者中SARS-CoV-2病毒RNA检测结果也更高。1例接受硼替佐米治疗的患者在这些细胞群体中出现了独特的变化。
所有接受mAB治疗的恶性肿瘤患者即使在存在B细胞缺陷的情况下，也对SARS-CoV-2产生了多功能免疫，包括体液免疫和T细胞免疫。这种免疫的演变，包括新变异株特异性抗体的产生，且未出现继发疾病，表明患者受到保护，免于出现有症状的再次感染，并且mAB疗法并未抑制宿主免疫的发展。未来有必要开展研究，以更好地描述随着时间推移接触新病毒变异株后的免疫记忆特征，评估病毒长期脱落情况以及对高危患者持续使用合适的mAB治疗感染的情况。
