Immunogenicity of COVID-19 Vaccinations in Hematological Patients: 6-Month Follow-Up and Evaluation of a 3rd Vaccination

被引:7
作者
Schubert, Lorenz [1 ]
Koblischke, Maximilian [2 ]
Schneider, Lisa [1 ]
Porpaczy, Edit [3 ]
Winkler, Florian [1 ,4 ]
Jaeger, Ulrich [3 ]
Bluml, Stephan [4 ]
Haslacher, Helmuth [5 ]
Burgmann, Heinz [1 ]
Aberle, Judith H. [2 ]
Winkler, Stefan [1 ]
Tobudic, Selma [1 ]
机构
[1] Med Univ Vienna, Dept Med 1, Div Infect Dis & Trop Med, A-1090 Vienna, Austria
[2] Med Univ Vienna, Ctr Virol, A-1090 Vienna, Austria
[3] Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, A-1090 Vienna, Austria
[4] Med Univ Vienna, Dept Med 3, Div Rheumatol, A-1090 Vienna, Austria
[5] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria
关键词
hematology-general; COVID-19; vaccine; clinical trials; T-CELL; RESPONSES; EFFICACY;
D O I
10.3390/cancers14081962
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary Here we confirm lower humoral and cellular responses in hematological patients compared with controls and highlight the response in risk-groups such as CAR-T-cell recipients. The main risk factor for a poor humoral response was anti-CD20 therapy. CD19(+) B-cell and CD4(+) T-cell levels were shown to be additional predictive markers for seroconversion. Further, we demonstrate a decline in antibodies over six months in responders and controls, and question if second vaccination non-responders benefit from of a third vaccination. Here we analyzed SARS-CoV-2-specific antibodies and T-cell responses after two coronavirus disease 2019 vaccinations over a six-month period in patients with hematological malignancies and assessed the effect of a third vaccination in a subgroup. Sixty-six patients and 66 healthy controls were included. After two vaccinations seroconversion was seen in 52% and a T-cell-specific response in 59% of patients compared with 100% in controls (p = 0.001). Risk factors for a poor serological response were age (<65a), history of anti-CD20 therapy within the year preceding vaccination, CD19(+) B-cells < 110/mu L, and CD4(+) T-cells > 310/mu L. The magnitude of T-cell response was higher in patients <65a and with CD19(+) B-cells < 110/mu L. Patients and healthy controls demonstrated a significant decrease in SARS-CoV-2 S antibody levels over the period of six months (p < 0.001). A third vaccination demonstrated a strong serological response in patients who had responded to the previous doses (p < 0.001). The third vaccination yielded seroconversion in three out of 19 patients in those without serological response. We conclude that both humoral and cellular responses after SARS-CoV-2 immunization are impaired in patients with hematological malignancies. A third vaccination enhanced B-cell response in patients who previously responded to the second vaccination but may be of limited benefit in patients without prior seroconversion.
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页数:13
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共 32 条
[1]   Suboptimal Response to Coronavirus Disease 2019 Messenger RNA Vaccines in Patients With Hematologic Malignancies: A Need for Vigilance in the Postmasking Era [J].
Agha, Mounzer E. ;
Blake, Maggie ;
Chilleo, Charles ;
Wells, Alan ;
Haidar, Ghady .
OPEN FORUM INFECTIOUS DISEASES, 2021, 8 (07)
[2]   Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine [J].
Baden, Lindsey R. ;
El Sahly, Hana M. ;
Essink, Brandon ;
Kotloff, Karen ;
Frey, Sharon ;
Novak, Rick ;
Diemert, David ;
Spector, Stephen A. ;
Rouphael, Nadine ;
Creech, C. Buddy ;
McGettigan, John ;
Khetan, Shishir ;
Segall, Nathan ;
Solis, Joel ;
Brosz, Adam ;
Fierro, Carlos ;
Schwartz, Howard ;
Neuzil, Kathleen ;
Corey, Larry ;
Gilbert, Peter ;
Janes, Holly ;
Follmann, Dean ;
Marovich, Mary ;
Mascola, John ;
Polakowski, Laura ;
Ledgerwood, Julie ;
Graham, Barney S. ;
Bennett, Hamilton ;
Pajon, Rolando ;
Knightly, Conor ;
Leav, Brett ;
Deng, Weiping ;
Zhou, Honghong ;
Han, Shu ;
Ivarsson, Melanie ;
Miller, Jacqueline ;
Zaks, Tal .
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (05) :403-416
[3]   CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer [J].
Bange, Erin M. ;
Han, Nicholas A. ;
Wileyto, Paul ;
Kim, Justin Y. ;
Gouma, Sigrid ;
Robinson, James ;
Greenplate, Allison R. ;
Hwee, Madeline A. ;
Porterfield, Florence ;
Owoyemi, Olutosin ;
Naik, Karan ;
Zheng, Cathy ;
Galantino, Michael ;
Weisman, Ariel R. ;
Ittner, Caroline A. G. ;
Kugler, Emily M. ;
Baxter, Amy E. ;
Oniyide, Olutwatosin ;
Agyekum, Roseline S. ;
Dunn, Thomas G. ;
Jones, Tiffanie K. ;
Giannini, Heather M. ;
Weirick, Madison E. ;
McAllister, Christopher M. ;
Babady, N. Esther ;
Kumar, Anita ;
Widman, Adam J. ;
DeWolf, Susan ;
Boutemine, Sawsan R. ;
Roberts, Charlotte ;
Budzik, Krista R. ;
Tollett, Susan ;
Wright, Carla ;
Perloff, Tara ;
Sun, Lova ;
Mathew, Divij ;
Giles, Josephine R. ;
Oldridge, Derek A. ;
Wu, Jennifer E. ;
Alanio, Cecile ;
Adamski, Sharon ;
Garfall, Alfred L. ;
Vella, Laura A. ;
Kerr, Samuel J. ;
Cohen, Justine, V ;
Oyer, Randall A. ;
Massa, Ryan ;
Maillard, Ivan P. ;
Maxwell, Kara N. ;
Reilly, John P. .
NATURE MEDICINE, 2021, 27 (07) :1280-+
[4]   Covid-19 in patients with chronic lymphocytic leukemia: clinical outcome and B- and T-cell immunity during 13 months in consecutive patients [J].
Blixt, Lisa ;
Bogdanovic, Gordana ;
Buggert, Marcus ;
Gao, Yu ;
Hober, Sophia ;
Healy, Katie ;
Johansson, Hemming ;
Kjellander, Christian ;
Mravinacova, Sara ;
Muschiol, Sandra ;
Nilsson, Peter ;
Palma, Marzia ;
Pin, Elisa ;
Smith, C. I. Edvard ;
Stromberg, Olga ;
Chen, Margaret Sallberg ;
Zain, Rula ;
Hansson, Lotta ;
Osterborg, Anders .
LEUKEMIA, 2022, 36 (02) :476-481
[5]   Chimeric antigen receptor T-cell therapies for lymphoma [J].
Brudno, Jennifer N. ;
Kochenderfer, James N. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2018, 15 (01) :31-46
[6]   Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 A Prospective Cohort Study [J].
Deepak, Parakkal ;
Kim, Wooseob ;
Paley, Michael A. ;
Yang, Monica ;
Carvidi, Alexander B. ;
Demissie, Emanuel G. ;
El-Qunni, Alia A. ;
Haile, Alem ;
Huang, Katherine ;
Kinnett, Baylee ;
Liebeskind, Mariel J. ;
Liu, Zhuoming ;
McMorrow, Lily E. ;
Paez, Diana ;
Pawar, Niti ;
Perantie, Dana C. ;
Schriefer, Rebecca E. ;
Sides, Shannon E. ;
Thapa, Mahima ;
Gergely, Mate ;
Abushamma, Suha ;
Akuse, Sewuese ;
Klebert, Michael ;
Mitchell, Lynne ;
Nix, Darren ;
Graf, Jonathan ;
Taylor, Kimberly E. ;
Chahin, Salim ;
Ciorba, Matthew A. ;
Katz, Patricia ;
Matloubian, Mehrdad ;
O'Halloran, Jane A. ;
Presti, Rachel M. ;
Wu, Gregory F. ;
Whelan, Sean P. J. ;
Buchser, William J. ;
Gensler, Lianne S. ;
Nakamura, Mary C. ;
Ellebedy, Ali H. ;
Kim, Alfred H. J. .
ANNALS OF INTERNAL MEDICINE, 2021, 174 (11) :1572-+
[7]   Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival [J].
Dispinseri, Stefania ;
Secchi, Massimiliano ;
Pirillo, Maria Franca ;
Tolazzi, Monica ;
Borghi, Martina ;
Brigatti, Cristina ;
De Angelis, Maria Laura ;
Baratella, Marco ;
Bazzigaluppi, Elena ;
Venturi, Giulietta ;
Sironi, Francesca ;
Canitano, Andrea ;
Marzinotto, Ilaria ;
Tresoldi, Cristina ;
Ciceri, Fabio ;
Piemonti, Lorenzo ;
Negri, Donatella ;
Cara, Andrea ;
Lampasona, Vito ;
Scarlatti, Gabriella .
NATURE COMMUNICATIONS, 2021, 12 (01)
[8]   Immune responses following third COVID-19 vaccination are reduced in patients with hematological compared to patients with solid cancer [J].
Fendler, Annika ;
Shepherd, Scott T. C. ;
Au, Lewis ;
Wilkinson, Katalin A. ;
Wu, Mary ;
Schmitt, Andreas M. ;
Tippu, Zayd ;
Farag, Sheima ;
Rogiers, Aljosja ;
Harvey, Ruth ;
Carlyle, Eleanor ;
Edmonds, Kim ;
Del Rosario, Lyra ;
Lingard, Karla ;
Mangwende, Mary ;
Holt, Lucy ;
Ahmod, Hamid ;
Korteweg, Justine ;
Foley, Tara ;
Barber, Taja ;
Emslie-Henry, Andrea ;
Caulfield-Lynch, Niamh ;
Byrne, Fiona ;
Shum, Benjamin ;
Gerard, Camille L. ;
Deng, Daqi ;
Kjaer, Svend ;
Song, Ok-Ryul ;
Queval, Christophe ;
Kavanagh, Caitlin ;
Wall, Emma C. ;
Carr, Edward J. ;
Namjou, Sina ;
Caidan, Simon ;
Gavrielides, Mike ;
MacRae, James I. ;
Kelly, Gavin ;
Peat, Kema ;
Kelly, Denise ;
Murra, Aida ;
Kelly, Kayleigh ;
O'Flaherty, Molly ;
Shea, Robyn L. ;
Gardner, Gail ;
Murray, Darren ;
Yousaf, Nadia ;
Jhanji, Shaman ;
Van As, Nicholas ;
Young, Kate ;
Furness, Andrew J. S. .
CANCER CELL, 2022, 40 (02) :114-116
[9]  
Garcia-Beltran WF, 2021, CELL, V184, P2372, DOI [10.1016/j.cell.2021.03.013, 10.1016/j.cell.2021.04.006, 10.1101/2021.02.14.21251704]
[10]   Waning Immunity after the BNT162b2 Vaccine in Israel [J].
Goldberg, Yair ;
Mandel, Micha ;
Bar-On, Yinon M. ;
Bodenheimer, Omri ;
Freedman, Laurence ;
Haas, Eric J. ;
Milo, Ron ;
Alroy-Preis, Sharon ;
Ash, Nachman ;
Huppert, Amit .
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 385 (24) :E85-E85