Colton Hayley, Barratt Natalie, Temperton Nigel, Hornsby Hailey, Angyal Adrienn, Grouneva Irina, Lindsey Benjamin B, Kearns Pamela, Barnes Eleanor, Goodyear Carl S, Richter Alex, Thomas David, Cook Gordon, McInnes Iain B, Willicombe Michelle, Siebert Stefan, Orchard Kim, Selby Rachael, Bowden Sarah, Collini Paul J, Pope Ann, Kirkham Amanda, Kronsteiner Barbara, Dunachie Susanna J, Miller Paul, Clay Jennifer, Hurst Erin, Malladi Ram, Kesavan Murali, Kinsella Francesca, Sanderson Robin, Yong Kwee L, Rea Daniel, Parry Helen, Lim Sean H, Snowden John A, de Silva Thushan I
Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK.
NIHR Sheffield Biomedical Research Centre and the Florey Institute of Infection, University of Sheffield, Sheffield, UK.
Br J Haematol. 2024 Dec;205(6):2206-2218. doi: 10.1111/bjh.19874. Epub 2024 Nov 17.
Whilst SARS-CoV-2 mRNA vaccines generate high neutralising antibodies (nAb) in most individuals, haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) recipients respond poorly. HSCT/CAR-T treatment ablates existing immune memory, with recipients requiring revaccination analogous to being vaccine naive. An optimal revaccination strategy for this cohort has not been defined. Factors predicting immunogenicity following three ancestral SARS-CoV-2 vaccines were assessed in 198 HSCT/CAR-T recipients and 96 healthcare workers (HCWs) recruited to multicentre studies. Only 25% of HSCT/CAR-T recipients generated nAbs following one dose, with titres 167-fold and 7-fold lower than that in HCWs after the first and second doses, respectively. Lower post-second dose nAb titres were associated with older age, rituximab use, and previous HSCT. ChAdOx1-S recipients were more likely to generate nAbs compared with mRNA vaccines, with titres comparable to HCWs. In contrast, nAbs were significantly lower in HSCT/CAR-T recipients than HCWs after mRNA vaccination. The poor first-dose immunogenicity in HSCT/CAR-T recipients suggests a minimum licensed dosing interval could limit the period of vulnerability following HSCT/CAR-T. The relative preservation of nAbs with ChAdOx1-S vaccination highlights the importance of evaluating alternative platforms to mRNA vaccination within this highly vulnerable clinical cohort.
虽然严重急性呼吸综合征冠状病毒2（SARS-CoV-2）信使核糖核酸（mRNA）疫苗能在大多数个体中产生高效中和抗体（nAb），但造血干细胞移植（HSCT）受者和嵌合抗原受体T细胞（CAR-T）受者的反应较差。HSCT/CAR-T治疗会消除现有的免疫记忆，受者需要重新接种疫苗，类似于初次接种疫苗的情况。尚未确定针对该队列的最佳重新接种策略。在198名HSCT/CAR-T受者和96名医护人员（HCW）中评估了三种原始SARS-CoV-2疫苗接种后预测免疫原性的因素，这些人员被招募参加多中心研究。只有25%的HSCT/CAR-T受者在接种一剂后产生了nAb，其滴度分别比医护人员在第一剂和第二剂后的滴度低167倍和7倍。第二剂后较低的nAb滴度与年龄较大、使用利妥昔单抗以及既往HSCT有关。与mRNA疫苗相比，接种ChAdOx1-S疫苗的受者更有可能产生nAb，其滴度与医护人员相当。相比之下，HSCT/CAR-T受者在接种mRNA疫苗后的nAb水平明显低于医护人员。HSCT/CAR-T受者首剂免疫原性较差表明，最低许可给药间隔可能会缩短HSCT/CAR-T后易感染期。ChAdOx1-S疫苗接种后nAb的相对保留凸显了在这个高度脆弱的临床队列中评估mRNA疫苗替代平台的重要性。
