Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors.
Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors.
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DOI：
10.1016/j.medj.2021.11.004
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发表时间：
2021-12-10
期刊：
影响因子：
--
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Chen RE;Gorman MJ;Zhu DY;Carreño JM;Yuan D;VanBlargan LA;Burdess S;Lauffenburger DA;Kim W;Turner JS;Droit L;Handley SA;Chahin S;Deepak P;O'Halloran JA;Paley MA;Presti RM;Wu GF;Krammer F;Alter G;Ellebedy AH;Kim AHJ;Diamond MS
虽然疫苗在健康个体中有效预防2019年冠状病毒病(新冠肺炎)，但在患有慢性炎症性疾病或接受慢性免疫抑制治疗的个体中，疫苗的免疫原性似乎较低。在这里，我们评估了77名接受慢性免疫抑制药物单一治疗的CID患者在BNT162b2mRNA疫苗免疫后血清中对历史和变异的严重急性呼吸综合征冠状病毒(SARS-CoV-2)病毒的抗体反应。纵向分析显示，在接受肿瘤坏死因子α(TnFi)抑制剂(α)治疗的患者中，中和抗体和Fc效应器功能能力的下降幅度最大，这种模式似乎对B.1.617.2 Delta病毒的效果更差。在接种疫苗的5个月内，所有接受TNFi治疗的受试者的血清中和效价都低于抗体介导保护的推定阈值。然而，接受第三次mRNA疫苗接种的接受TNFi治疗的人，他们的血清中和抗体效价提高了16倍以上。可能需要加强疫苗接种或实施长效预防措施(例如，单抗)，以防止在这一易感人群中感染SARS-CoV-2。这项研究得到了美国国立卫生研究院的赠款和合同的支持(R01 AI157155、R01AI151178和HHSN75N93019C00074；NIAID流感研究和反应英才中心(CEIRR)合同HHSN272201400008C和75N93021C00014；以及合作流感疫苗创新中心[公民]合同75N93019C00051)。在大多数人中，mRNA疫苗有效地预防了SARS-CoV-2感染后的严重疾病。然而，在免疫低下的个体中，mRNA疫苗诱导的保护性免疫作用减弱，变异株的作用尚不清楚。在这里，我们评估了慢性炎症性疾病患者在接种辉瑞BNT162b2mRNA疫苗后的血清抗体反应。在接受肿瘤坏死因子-α抑制剂治疗的患者中，观察到中和抗体效价最低，这种模式似乎对Delta病毒更糟糕，抗体水平降至假定的保护阈值以下。接种第三剂疫苗可显著提高血清中和效价。我们的数据表明，在一些免疫功能低下的人群中，特别是那些接受肿瘤坏死因子-α抑制剂治疗的人群中，需要加强疫苗接种以防止SARS-CoV-2感染。Chen等人。评估接受单一免疫抑制药物治疗的慢性炎症性疾病患者接受BNT162b2mRNA疫苗接种后的血清抗体。接受肿瘤坏死因子-α抑制剂的个体对B.1.351和B.1.617.2变异体的抗体中和和Fc效应功能活性降低。第三剂疫苗显著提高了TNFi接受者的中和滴度。
Although vaccines effectively prevent coronavirus disease 2019 (COVID-19) in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy. Here we assessed a cohort of 77 individuals with CID treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses after immunization with the BNT162b2 mRNA vaccine. Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with tumor necrosis factor alpha (TNF-α) inhibitors (TNFi), and this pattern appeared to be worse against the B.1.617.2 delta virus. Within 5 months of vaccination, serum neutralizing titers of all TNFi-treated individuals tested fell below the presumed threshold correlate for antibody-mediated protection. However, TNFi-treated individuals receiving a third mRNA vaccine dose boosted their serum neutralizing antibody titers by more than 16-fold. Vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) will likely be required to prevent SARS-CoV-2 infection in this susceptible population. This study was supported by grants and contracts from the NIH (R01 AI157155, R01AI151178, and HHSN75N93019C00074; NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C and 75N93021C00014; and Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051). In most individuals, mRNA vaccines effectively prevent severe disease following SARS-CoV-2 infection. However, the protective immunity induced by mRNA vaccines is diminished in immunocompromised individuals, and the effect of variant strains is unexplored. Here we evaluated serum antibody responses in individuals with chronic inflammatory disease after immunization with the Pfizer BNT162b2 mRNA vaccine. The lowest neutralizing antibody titers were observed in individuals treated with TNF-α inhibitors, and this pattern appeared to be worse against the delta virus, with the antibody levels falling below the presumed threshold correlate of protection. Administration of a third vaccine dose substantially boosted serum neutralizing titers. Our data suggest that vaccine boosting is needed to prevent SARS-CoV-2 infection in some immunocompromised populations, especially those receiving TNF-α inhibitor therapies. Chen et al. assess serum antibodies from BNT162b2 mRNA-vaccinated individuals with chronic inflammatory disease receiving single immunosuppressive drug therapies. Individuals receiving TNF-α inhibitors (TNFi) had reduced antibody neutralizing and Fc effector function activity against the B.1.351 and B.1.617.2 variants. A third vaccine dose markedly boosted neutralizing titers in TNFi recipients.
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影响因子：
24.5
作者：
Cullen, Garret;Bader, Caroline;Sands, Bruce E.
通讯作者：
Sands, Bruce E.
影响因子：
3.7
作者：
Chan CEZ;Seah SGK;Chye H;Massey S;Torres M;Lim APC;Wong SKK;Neo JJY;Wong PS;Lim JH;Loh GSL;Wang D;Boyd-Kirkup JD;Guan S;Thakkar D;Teo GH;Purushotorman K;Hutchinson PE;Young BE;Low JG;MacAry PA;Hentze H;Prativadibhayankara VS;Ethirajulu K;Comer JE;Tseng CK;Barrett ADT;Ingram PJ;Brasel T;Hanson BJ
通讯作者：
Hanson BJ
DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
影响因子：
82.9
作者：
Chemaitelly, Hiam;Yassine, Hadi M.;Abu-Raddad, Laith J.
通讯作者：
Abu-Raddad, Laith J.
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F