Hill Joshua A, Martens Michael J, Young Jo-Anne H, Bhavsar Kavita, Kou Jianqun, Chen Min, Lee Lik Wee, Baluch Aliyah, Dhodapkar Madhav V, Nakamura Ryotaro, Peyton Kristin, Howard Dianna S, Ibrahim Uroosa, Shahid Zainab, Armistead Paul, Westervelt Peter, McCarty John, McGuirk Joseph, Hamadani Mehdi, DeWolf Susan, Hosszu Kinga, Sharon Elad, Spahn Ashley, Toor Amir A, Waldvogel Stephanie, Greenberger Lee M, Auletta Jeffery J, Horowitz Mary M, Riches Marcie L, Perales Miguel-Angel
Vaccine and Infectious Disease, Fred Hutchinson Cancer Center, and Department of Medicine, University of Washington, Seattle, WA, USA.
Center for International Blood and Marrow Transplantation Research, Medical College of Wisconsin, Milwaukee, WI, USA.
medRxiv. 2024 Jan 25:2024.01.24.24301058. doi: 10.1101/2024.01.24.24301058.
The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood.
To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy.
Multicenter prospective observational study.
34 centers in the United States.
466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022.
SARS-CoV-2 vaccination as part of routine care.
We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup.
Anti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell recipients initiating vaccines within 4 months. Anti-S IgG 2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels.
The majority of participants were adults and received mRNA vaccines.
These data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy.
National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.
细胞治疗后接种新型冠状病毒2（SARS-CoV-2）疫苗的最佳时机尚未完全明确。
描述在细胞治疗后不到4个月与4至12个月开始接种SARS-CoV-2疫苗后的体液和细胞反应。
多中心前瞻性观察性研究。
美国34个中心。
2021年4月至2022年6月期间登记的466例异基因造血细胞移植（HCT；n = 231）、自体HCT（n = 170）或嵌合抗原受体T细胞（CAR-T细胞）治疗（n = 65）的接受者。
将SARS-CoV-2疫苗接种作为常规护理的一部分。
我们在多达五个时间点的接种前和接种后采集血液，检测所有参与者的SARS-CoV-2刺突蛋白（抗S）IgG，并在一个亚组中检测针对武汉D614G、德尔塔B.1.617.2和奥密克戎B.1.1.529毒株的中和抗体，以及SARS-CoV-2特异性T细胞受体（TCR）。
无论疫苗接种开始时间如何，HCT接受者接种疫苗后抗S IgG和中和抗体反应均增加，但在4个月内开始接种疫苗的CAR-T细胞接受者中无变化。抗S IgG 2500 U/mL与高中和抗体滴度相关，在异基因HCT、自体HCT和CAR-T细胞接受者中，分别有70%、69%和34%在最后一个时间点达到该水平。SARS-CoV-2特异性T细胞反应分别在57%、83%和58%的接受者中出现。在细胞治疗后不到4个月与4至12个月开始接种疫苗的参与者之间，体液和细胞反应无显著差异。细胞治疗前的SARS-CoV-2感染或疫苗接种是细胞治疗后抗S IgG水平的关键预测因素。
大多数参与者为成年人且接受了mRNA疫苗。
这些数据支持在异基因HCT、自体HCT和CAR-T细胞治疗后三到四个月开始接种mRNA SARS-CoV-2疫苗。
国家骨髓捐献者计划、白血病和淋巴瘤协会、多发性骨髓瘤研究基金会、诺华公司、LabCorp、美国移植和细胞治疗学会、Adaptive Biotechnologies以及美国国立卫生研究院。
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