Reduced Antibodies and Innate Cytokine Changes in SARS-CoV-2 BNT162b2 mRNA Vaccinated Transplant Patients With Hematological Malignancies

被引:11
作者
Bergamaschi, Cristina [1 ]
Pagoni, Maria [2 ,8 ]
Rosati, Margherita [3 ]
Angel, Matthew [4 ,5 ]
Tzannou, Ifigeneia [2 ,8 ]
Vlachou, Margarita [6 ]
Darmani, Ismini [2 ,8 ]
Ullah, Amirah [1 ]
Bear, Jenifer [1 ]
Devasundaram, Santhi [1 ]
Burns, Robert [1 ]
Baltadakis, Ioannis [2 ,8 ]
Gigantes, Stavros [2 ,8 ]
Dimopoulos, Meletios-Athanasios [7 ]
Pavlakis, George N. [3 ]
Terpos, Evangelos [7 ]
Felber, Barbara K. [1 ]
机构
[1] Natl Canc Inst Frederick, Ctr Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD 21702 USA
[2] Evangelismos Gen Hosp, Dept Hematol & Lymphomas, Athens, Greece
[3] Natl Canc Inst Frederick, Ctr Canc Res, Human Retrovirus Sect, Vaccine Branch, Frederick, MD USA
[4] NCI, Ctr Canc Res, Vaccine Branch, Bethesda, MD USA
[5] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Ctr Canc Res Collaborat Bioinformat Resource, Frederick, MD USA
[6] Evangelismos Gen Hosp, Pharm Dept, Athens, Greece
[7] Natl & Kapodistrian Univ Athens, Sch Med, Dept Clin Therapeut, Athens, Greece
[8] Evangelismos Gen Hosp, Bone Marrow Transplantat Unit, Athens, Greece
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
美国国家卫生研究院;
关键词
humoral response; cytokine; SARS-CoV-2 BNT162b2 mRNA vaccine; IFN-gamma; CXCL10; IL-15; transplantation; hematological cancer; YELLOW-FEVER VACCINE; COVID-19; VACCINE; IMMUNOGENICITY; RESPONSES;
D O I
10.3389/fimmu.2022.899972
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunocompromised individuals including patients with hematological malignancies constitute a population at high risk of developing severe disease upon SARS-CoV-2 infection. Protection afforded by vaccination is frequently low and the biology leading to altered vaccine efficacy is not fully understood. A patient cohort who had received bone marrow transplantation or CAR-T cells was studied following a 2-dose BNT162b2 mRNA vaccination and compared to healthy vaccine recipients. Anti-Spike antibody and systemic innate responses were compared in the two vaccine cohorts. The patients had significantly lower SARS-CoV-2 Spike antibodies to the Wuhan strain, with proportional lower cross-recognition of Beta, Delta, and Omicron Spike-RBD proteins. Both cohorts neutralized the wildtype WA1 and Delta but not Omicron. Vaccination elicited an innate cytokine signature featuring IFN-gamma, IL-15 and IP-10/CXCL10, but most patients showed a diminished systemic cytokine response. In patients who failed to develop antibodies, the innate systemic response was dominated by IL-8 and MIP-1 alpha with significant attenuation in the IFN-gamma, IL-15 and IP-10/CXCL10 signature response. Changes in IFN-gamma and IP-10/CXCL10 at priming vaccination and IFN-gamma, IL-15, IL-7 and IL-10 upon booster vaccination correlated with the Spike antibody magnitude and were predictive of successful antibody development. Overall, the patients showed heterogeneous adaptive and innate responses with lower humoral and reduced innate cytokine responses to vaccination compared to naive vaccine recipients. The pattern of responses described offer novel prognostic approaches for potentiating the effectiveness of COVID-19 vaccination in transplant patients with hematological malignancies.
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页数:17
相关论文
共 45 条
[11]   Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses [J].
Gaucher, Denis ;
Therrien, Rene ;
Kettaf, Nadia ;
Angermann, Bastian R. ;
Boucher, Genevieve ;
Filali-Mouhim, Abdelali ;
Moser, Janice M. ;
Mehta, Riyaz S. ;
Drake, Donald R., III ;
Castro, Erika ;
Akondy, Rama ;
Rinfret, Aline ;
Yassine-Diab, Bader ;
Said, Elias A. ;
Chouikh, Younes ;
Cameron, Mark J. ;
Clum, Robert ;
Kelvin, David ;
Somogyi, Roland ;
Greller, Larry D. ;
Balderas, Robert S. ;
Wilkinson, Peter ;
Pantaleo, Giuseppe ;
Tartaglia, Jim ;
Haddad, Elias K. ;
Sekaly, Rafick-Pierre .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (13) :3119-3131
[12]   Poor neutralizing antibody responses in 106 patients with WM after vaccination against SARS-CoV-2: a prospective study [J].
Gavriatopoulou, Maria ;
Terpos, Evangelos ;
Ntanasis-Stathopoulos, Ioannis ;
Briasoulis, Alexandros ;
Gumeni, Sentiljana ;
Malandrakis, Panagiotis ;
Fotiou, Despina ;
Migkou, Magdalini ;
Theodorakakou, Foteini ;
Eleutherakis-Papaiakovou, Evangelos ;
Kanellias, Nikolaos ;
Kastritis, Efstathios ;
Trougakos, Ioannis P. ;
Dimopoulos, Meletios A. .
BLOOD ADVANCES, 2021, 5 (21) :4398-4405
[13]   Myeloma patients with COVID-19 have superior antibody responses compared to patients fully vaccinated with the BNT162b2 vaccine [J].
Gavriatopoulou, Maria ;
Terpos, Evangelos ;
Malandrakis, Panagiotis ;
Ntanasis-Stathopoulos, Ioannis ;
Briasoulis, Alexandros ;
Gumeni, Sentiljana ;
Fotiou, Despina ;
Papanagnou, Eleni-Dimitra ;
Migkou, Magdalini ;
Theodorakakou, Foteini ;
Eleutherakis-Papaiakovou, Evangelos ;
Kanellias, Nikolaos ;
Trougakos, Ioannis P. ;
Kastritis, Efstathios ;
Dimopoulos, Meletios-Athanasios .
BRITISH JOURNAL OF HAEMATOLOGY, 2022, 196 (02) :356-359
[14]   Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies [J].
Greenberger, Lee M. ;
Saltzman, Larry A. ;
Senefeld, Jonathon W. ;
Johnson, Patrick W. ;
DeGennaro, Louis J. ;
Nichols, Gwen L. .
CANCER CELL, 2021, 39 (08) :1031-1033
[15]   Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination [J].
Herishanu, Yair ;
Rahav, Galia ;
Levi, Shai ;
Braester, Andrei ;
Itchaki, Gilad ;
Bairey, Osnat ;
Dally, Najib ;
Shvidel, Lev ;
Ziv-Baran, Tomer ;
Polliack, Aaron ;
Tadmor, Tamar ;
Benjamini, Ohad .
BLOOD, 2022, 139 (05) :678-685
[16]  
Knabl Ludwig, 2021, Res Sq, DOI 10.21203/rs.3.rs-509143/v1
[17]   Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients [J].
Liebers, Nora ;
Speer, Claudius ;
Benning, Louise ;
Bruch, Peter -Martin ;
Kraemer, Isabelle ;
Meissner, Julia ;
Schnitzler, Paul ;
eurousslich, Hans-Georg Kra ;
Dreger, Peter ;
Mueller-Tidow, Carsten ;
Poschke, Isabel ;
Dietrich, Sascha .
BLOOD, 2022, 139 (01) :142-147
[18]   Antibody responses to SARS-CoV-2 in patients with COVID-19 [J].
Long, Quan-Xin ;
Liu, Bai-Zhong ;
Deng, Hai-Jun ;
Wu, Gui-Cheng ;
Deng, Kun ;
Chen, Yao-Kai ;
Liao, Pu ;
Qiu, Jing-Fu ;
Lin, Yong ;
Cai, Xue-Fei ;
Wang, De-Qiang ;
Hu, Yuan ;
Ren, Ji-Hua ;
Tang, Ni ;
Xu, Yin-Yin ;
Yu, Li-Hua ;
Mo, Zhan ;
Gong, Fang ;
Zhang, Xiao-Li ;
Tian, Wen-Guang ;
Hu, Li ;
Zhang, Xian-Xiang ;
Xiang, Jiang-Lin ;
Du, Hong-Xin ;
Liu, Hua-Wen ;
Lang, Chun-Hui ;
Luo, Xiao-He ;
Wu, Shao-Bo ;
Cui, Xiao-Ping ;
Zhou, Zheng ;
Zhu, Man-Man ;
Wang, Jing ;
Xue, Cheng-Jun ;
Li, Xiao-Feng ;
Wang, Li ;
Li, Zhi-Jie ;
Wang, Kun ;
Niu, Chang-Chun ;
Yang, Qing-Jun ;
Tang, Xiao-Jun ;
Zhang, Yong ;
Liu, Xia-Mao ;
Li, Jin-Jing ;
Zhang, De-Chun ;
Zhang, Fan ;
Liu, Ping ;
Yuan, Jun ;
Li, Qin ;
Hu, Jie-Li ;
Chen, Juan .
NATURE MEDICINE, 2020, 26 (06) :845-+
[19]   Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies [J].
Malard, Florent ;
Gaugler, Beatrice ;
Gozlan, Joel ;
Bouquet, Lucie ;
Fofana, Djeneba ;
Siblany, Lama ;
Eshagh, Deborah ;
Adotevi, Olivier ;
Laheurte, Caroline ;
Ricard, Laure ;
Dulery, Remy ;
Stocker, Nicolas ;
van de Wyngaert, Zoe ;
Genthon, Alexis ;
Banet, Anne ;
Memoli, Mara ;
Ikhlef, Souhila ;
Sestilli, Simona ;
Vekhof, Anne ;
Brissot, Eolia ;
Marjanovic, Zora ;
Chantran, Yannick ;
Cuervo, Nancy ;
Ballot, Eric ;
Morand-Joubert, Laurence ;
Mohty, Mohamad .
BLOOD CANCER JOURNAL, 2021, 11 (08)
[20]   Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera [J].
Muik, Alexander ;
Lui, Bonny Gaby ;
Wallisch, Ann-Kathrin ;
Bacher, Maren ;
Muehl, Julia ;
Reinholz, Jonas ;
Ozhelvaci, Orkun ;
Beckmann, Nina ;
Garcia, Ramon de la Caridad Gueimil ;
Poran, Asaf ;
Shpyro, Svetlana ;
Finlayson, Andrew ;
Cai, Hui ;
Yang, Qi ;
Swanson, Kena A. ;
Tuereci, Oezlem ;
Sahin, Ugur .
SCIENCE, 2022, 375 (6581) :678-+