Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido 060-0808, Japan.
Cell Rep Med. 2023 Apr 18;4(4):101017. doi: 10.1016/j.xcrm.2023.101017. Epub 2023 Mar 27.
Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%-75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4/CD8 T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.
免疫功能低下的血液学患者易患重症 COVID-19，且对疫苗接种的反应较差。然而，相对免疫缺陷尚不清楚，尤其是在接种 3 剂疫苗之后。我们评估了 COVID-19 接种 3 剂疫苗后血液学患者的免疫反应。BNT162b2 和 ChAdOx1 接种一剂后的血清阳性率较低（约 26%），第二剂后增加至 59%-75%，第三剂后增加至 85%。虽然在健康参与者中可引发典型的抗体分泌细胞（ASC）和滤泡辅助 T 细胞（Tfh）反应，但血液学患者表现出 ASC 延长和 Tfh2/17 反应偏向。重要的是，无论 B 细胞数量如何，疫苗诱导的 Spike 特异性和肽-HLA 四聚体特异性 CD4/CD8 T 细胞的扩增及其 TCR 谱在血液学患者中均是强大的，与健康参与者相当。突破性感染的接种患者产生了更高的抗体反应，而 T 细胞反应与健康组相当。COVID-19 疫苗接种可在不同疾病和治疗的血液学患者中诱导出强大的 T 细胞免疫，而与 B 细胞数量和抗体反应无关。
