Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients: A Randomized Clinical Trial.
Comparison of SARS-CoV-2 Antibody Response 4 Weeks After Homologous vs Heterologous Third Vaccine Dose in Kidney Transplant Recipients: A Randomized Clinical Trial.
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DOI：
10.1001/jamainternmed.2021.7372
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发表时间：
2022-02-01
影响因子：
39
通讯作者：
Oberbauer R
中科院分区：
文献类型：
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作者：
Reindl-Schwaighofer R;Heinzel A;Mayrdorfer M;Jabbour R;Hofbauer TM;Merrelaar A;Eder M;Regele F;Doberer K;Spechtl P;Aschauer C;Koblischke M;Paschen C;Eskandary F;Hu K;Öhler B;Bhandal A;Kleibenböck S;Jagoditsch RI;Reiskopf B;Heger F;Bond G;Böhmig GA;Strassl R;Weseslindtner L;Indra A;Aberle JH;Binder M;Oberbauer R
与同源第三剂 mRNA 疫苗（mRNA-1273 或 BNT162b2）相比，在接受 2 剂 mRNA 疫苗后未产生 SARS-CoV-2 抗体的肾移植受者中，使用载体疫苗 Ad26COVS1 的异源 SARS-CoV-2 疫苗接种策略是否会产生更高的抗体反应率？这项随机临床试验发现，在 197 名没有抗体的肾移植受者中接种 2 剂 mRNA 疫苗后，再注射第三剂 SARS-CoV-2 疫苗，同源（mRNA）组中有 35% 的人产生了抗体反应，而异源（载体）组中有 42% 的人产生了抗体反应，但没有统计学上的显着差异。这项随机临床试验的结果表明，肾移植受者中第三剂 SARS-CoV-2 疫苗的同源和异源疫苗接种策略具有可比性，mRNA 和载体疫苗在超过三分之一的肾移植受者中实现了血清转化。然而，鉴于第三次给药后无反应者比例很高，迫切需要在肾移植受者中诱导免疫反应的其他策略。不到 50% 的肾移植受者 (KTR) 在注射 2 剂 mRNA 疫苗后产生针对 SARS-CoV-2 刺突蛋白的抗体。初步数据表明，结合 mRNA 和病毒载体疫苗的异源疫苗可能会增加免疫原性。旨在评估第三剂 mRNA 与载体疫苗对 KTR 的有效性，这些 KTR 在接受 2 剂 mRNA 疫苗后没有针对 SARS-CoV-2 刺突蛋白的抗体。这是一项针对第三剂 SARS-CoV-2 疫苗的单中心、单盲、1:1 随机临床试验，于 2021 年 6 月 15 日至 8 月 16 日在 201 名 KTR 中进行，这些 KTR 在注射 2 剂 mRNA 疫苗后尚未产生 SARS-CoV-2 刺突蛋白抗体。数据分析于2021年8月17日至8月31日进行。mRNA（BNT162b2或mRNA-1273）或载体（Ad26COVS1）作为第三剂SARS-CoV-2疫苗。主要研究终点是第三剂疫苗接种后 4 周（29-42 天）后的血清转化。次要终点包括通过干扰素-γ释放测定（IGRA）评估的中和抗体和 T 细胞反应。此外，使用逻辑回归评估患者特征和疫苗反应的关联，并比较疫苗的反应原性。在 197 名肾移植受者的研究人群中（平均 [SD] 年龄，61.2 [12.4] 岁；82 名 [42%] 女性），39% 的人在第三次疫苗接种后产生了 SARS-CoV-2 抗体。各组之间没有统计学上的显着差异，mRNA 和载体疫苗的抗体应答率分别为 35% 和 42%。只有 22% 的血清转化患者具有中和抗体。同样，IGRA 评估的 T 细胞反应较低，只有 17 名患者在第三次疫苗接种后表现出阳性反应。接受非三重免疫抑制（比值比 [OR]，3.59；95% CI，1.33-10.75）、肾移植后较长时间（OR，1.44；95% CI，1.15-1.83，每翻一番）和扭矩腱病毒血浆水平（OR，0.92；95% CI，0.88-0.96）水平加倍）与疫苗反应有关。与载体疫苗相比，第三剂 mRNA 疫苗与注射部位局部疼痛的频率更高有关，而各组之间的全身症状相当。这项随机临床试验发现，在注射 2 剂 mRNA 疫苗后，39% 的 KTR 没有针对 SARS-CoV-2 产生免疫反应，在注射第三剂 mRNA 或载体疫苗 4 周后，39% 的 KTR 产生了针对 SARS-CoV-2 刺突蛋白的抗体。基于载体的疫苗的异源疫苗接种策略具有良好的耐受性和安全性，但并不明显优于基于同源 mRNA 的策略。 EudraCT 标识符：2021-002927-39 这项随机临床试验评估了 201 名没有 SARS-CoV-2 抗体的肾移植受者在接受 2 剂 mRNA 疫苗后，第三剂基于 mRNA 的疫苗与基于载体的疫苗的有效性。
Does a heterologous SARS-CoV-2 vaccination strategy with the vector vaccine Ad26COVS1 result in a higher rate of antibody response compared with a homologous third dose of mRNA vaccine (mRNA-1273 or BNT162b2) in kidney transplant recipients who did not develop SARS-CoV-2 antibodies after 2 doses of an mRNA vaccine? This randomized clinical trial found that a third dose of SARS-CoV-2 vaccine in 197 kidney transplant recipients without antibodies after 2 doses of an mRNA vaccine induced an antibody response in 35% of the homologous (mRNA) group vs 42% of the heterologous (vector) group, with no statistically significant difference. The findings of this randomized clinical trial show that homologous and heterologous vaccination strategies for a third SARS-CoV-2 vaccine dose in kidney transplant recipients are comparable, with both mRNA and vector vaccines achieving seroconversion in more than one-third of kidney transplant recipients. However, given the high rate of nonresponders after the third dose, additional strategies to induce an immune response in kidney transplant recipients are urgently needed. Fewer than 50% of kidney transplant recipients (KTRs) develop antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine. Preliminary data suggest that a heterologous vaccination, combining mRNA and viral vector vaccines, may increase immunogenicity. To assess the effectiveness of a third dose of an mRNA vs a vector vaccine in KTRs who did not have antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine. This was a single center, single-blinded, 1:1 randomized clinical trial of a third dose of vaccine against SARS-CoV-2, conducted from June 15 to August 16, 2021, in 201 KTRs who had not developed SARS-CoV-2 spike protein antibodies after 2 doses of an mRNA vaccine. Data analyses were performed from August 17 to August 31, 2021. mRNA (BNT162b2 or mRNA-1273) or vector (Ad26COVS1) as a third dose of a SARS-CoV-2 vaccine. The primary study end point was seroconversion after 4 weeks (29-42 days) following the third vaccine dose. Secondary end points included neutralizing antibodies and T-cell response assessed by interferon-γ release assays (IGRA). In addition, the association of patient characteristics and vaccine response was assessed using logistic regression, and the reactogenicity of the vaccines was compared. Among the study population of 197 kidney transplant recipients (mean [SD] age, 61.2 [12.4] years; 82 [42%] women), 39% developed SARS-CoV-2 antibodies after the third vaccine. There was no statistically significant difference between groups, with an antibody response rate of 35% and 42% for the mRNA and vector vaccines, respectively. Only 22% of seroconverted patients had neutralizing antibodies. Similarly, T-cell response assessed by IGRA was low with only 17 patients showing a positive response after the third vaccination. Receiving nontriple immunosuppression (odds ratio [OR], 3.59; 95% CI, 1.33-10.75), longer time after kidney transplant (OR, 1.44; 95% CI, 1.15-1.83, per doubling of years), and torque teno virus plasma levels (OR, 0.92; 95% CI, 0.88-0.96, per doubling of levels) were associated with vaccine response. The third dose of an mRNA vaccine was associated with a higher frequency of local pain at the injection site compared with the vector vaccine, while systemic symptoms were comparable between groups. This randomized clinical trial found that 39% of KTRs without an immune response against SARS-CoV-2 after 2 doses of an mRNA vaccine developed antibodies against the SARS-CoV-2 spike protein 4 weeks after a third dose of an mRNA or a vector vaccine. The heterologous vaccination strategy with a vector-based vaccine was well tolerated and safe but not significantly better than the homologous mRNA-based strategy. EudraCT Identifier: 2021-002927-39 This randomized clinical trial evaluated the effectiveness of a third dose of mRNA-based vs a vector-based vaccine in 201 kidney transplant recipients with no SARS-CoV-2 antibodies after 2 prior doses of an mRNA vaccine.
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DOI：
10.1111/ajt.16460
发表时间：
2021-07
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
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作者：
Nair V;Jandovitz N;Hirsch JS;Abate M;Satapathy SK;Roth N;Miyara SJ;Guevara S;Kressel AM;Xiang A;Wu G;Butensky SD;Lin D;Williams S;Bhaskaran MC;Majure DT;Grodstein E;Lau L;Nair G;Fahmy AE;Winnick A;Breslin N;Berlinrut I;Molmenti C;Becker LB;Malhotra P;Gautam-Goyal P;Lima B;Maybaum S;Shah SK;Takegawa R;Hayashida K;Shinozaki K;Teperman LW;Molmenti EP;Northwell Health COVID-19 Research Consortium
通讯作者：
Northwell Health COVID-19 Research Consortium
影响因子：
8.8
作者：
Grupper, Ayelet;Rabinowich, Liane;Katchman, Helena
通讯作者：
Katchman, Helena
影响因子：
2.6
作者：
Hosseini-Moghaddam, S. M.;Alhomayeed, B.;House, A. A.
通讯作者：
House, A. A.
影响因子：
82.9
作者：
Schmidt T;Klemis V;Schub D;Mihm J;Hielscher F;Marx S;Abu-Omar A;Ziegler L;Guckelmus C;Urschel R;Schneitler S;Becker SL;Gärtner BC;Sester U;Sester M
通讯作者：
Sester M
DOI：
10.1056/nejmoa2101544
发表时间：
2021-06-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sadoff J;Gray G;Vandebosch A;Cárdenas V;Shukarev G;Grinsztejn B;Goepfert PA;Truyers C;Fennema H;Spiessens B;Offergeld K;Scheper G;Taylor KL;Robb ML;Treanor J;Barouch DH;Stoddard J;Ryser MF;Marovich MA;Neuzil KM;Corey L;Cauwenberghs N;Tanner T;Hardt K;Ruiz-Guiñazú J;Le Gars M;Schuitemaker H;Van Hoof J;Struyf F;Douoguih M;ENSEMBLE Study Group
通讯作者：
ENSEMBLE Study Group