Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial.
Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial.
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DOI：
10.1016/j.ebiom.2021.103705
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发表时间：
2021-12
期刊：
影响因子：
11.1
通讯作者：
COVAXID-collaborator group (shown separately)
中科院分区：
文献类型：
--
作者：
Bergman P;Blennow O;Hansson L;Mielke S;Nowak P;Chen P;Söderdahl G;Österborg A;Smith CIE;Wullimann D;Vesterbacka J;Lindgren G;Blixt L;Friman G;Wahren-Borgström E;Nordlander A;Gomez AC;Akber M;Valentini D;Norlin AC;Thalme A;Bogdanovic G;Muschiol S;Nilsson P;Hober S;Loré K;Chen MS;Buggert M;Ljunggren HG;Ljungman P;Aleman S;COVAXID-collaborator group (shown separately)
免疫功能低下疾病患者主要被排除在COVID-19疫苗接种的临床试验之外。因此，该前瞻性临床试验的目的是在五组选定的免疫功能低下患者和健康对照中研究BNT 162 b2 mRNA疫苗接种的安全性和有效性。纳入了539例研究受试者（449例患者和90例对照）。患者患有原发性（n=90）或继发性免疫缺陷疾病，原因包括人类免疫缺陷病毒感染（n=90）、异基因造血干细胞移植/CAR T细胞治疗（n=90）、实体器官移植（SOT）（n=89）或慢性淋巴细胞白血病（CLL）（n=90）。主要终点是第二剂后两周的血清转换率。次要终点是安全性和记录的SARS-CoV-2感染。不良事件一般为轻度，但发生1例致死性疑似非预期严重不良反应。72.2%的免疫功能低下患者血清转化，而对照组为100%（p=0.004）。SOT（43.4%）和CLL（63.3%）患者组的血清转换率最低，分别观察到霉酚酸酯和伊曲替尼治疗的负面影响。结果表明，mRNA BNT 162 b2疫苗在免疫功能低下的患者中是安全的。血清转化率显著低于健康对照，在预定义的患者组和亚组中，血清转化率和抗体滴度范围很广。这项临床试验强调了在某些免疫功能低下的患者群体中需要额外的疫苗剂量来提高免疫力。Knut和Alice Wallenberg基金会、瑞典研究理事会、Nordstjernan AB、斯德哥尔摩地区、Karolinska Institutet和瑞典PID/CLL患者组织。
Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.
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影响因子：
20.3
作者：
Dhakal B;Abedin S;Fenske T;Chhabra S;Ledeboer N;Hari P;Hamadani M
通讯作者：
Hamadani M
BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
影响因子：
25.7
作者：
Rabinowich L;Grupper A;Baruch R;Ben-Yehoyada M;Halperin T;Turner D;Katchman E;Levi S;Houri I;Lubezky N;Shibolet O;Katchman H
通讯作者：
Katchman H
影响因子：
12.8
作者：
Herzog Tzarfati, Katrin;Gutwein, Odit;Koren-Michowitz, Maya
通讯作者：
Koren-Michowitz, Maya
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group