Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial.
Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial.
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DOI：
10.1038/s41591-022-01739-w
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发表时间：
2022-05
期刊：
影响因子：
82.9
通讯作者：
McPhee, Roderick
中科院分区：
文献类型：
--
作者：
Chu, Laurence;Vrbicky, Keith;Montefiori, David;Huang, Wenmei;Nestorova, Biliana;Chang, Ying;Carfi, Andrea;Edwards, Darin K.;Oestreicher, Judy;Legault, Holly;Dutko, Frank J.;Girard, Bethany;Pajon, Rolando;Miller, Jacqueline M.;Das, Rituparna;Leav, Brett;McPhee, Roderick
先前免疫过的个体中严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的突破性感染不断增加，引发了人们对是否需要加强疫苗剂量来对抗抗体水平下降和新变种的担忧。在此，我们报告了一项 2 期试验的开放标签、非随机 B 部分的结果，在该试验中，我们评估了 344 名成年参与者加强注射 50 µg 2019 年冠状病毒病 (COVID-19) 疫苗 mRNA-1273 的安全性和免疫原性，这些参与者在 6 至 8 个月前接受了两剂 50 µg 或 100 µg 疫苗的初级系列免疫。 mRNA-1273 (NCT04405076)。加强注射后 1 个月时，针对野生型 SARS-CoV-2 的中和抗体 (nAb) 滴度比第二次注射初级系列后 28 天时高 1.7 倍（95% 置信区间 (CI)：1.5、1.9），符合预先指定的非劣效性标准（初级免疫原性目标），并可能表明记忆 B 细胞反应。加强注射后 1 个月时，针对 Delta 变体 (B.1.617.2)（探索性目标）的 nAb 滴度比初次注射第二次注射后 28 天时的 nAb 滴度高 2.1 倍（95% CI：1.8，2.4）。加强接种后 28 天的血清反应率（95% CI（较基线上升四倍））为 100% (98.7, 100.0)，而初次接种后的血清反应率为 98.3% (96.0, 99.4)。在 3 期 COVE 研究中，在通过 ELISA 和 Meso Scale Discovery (MSD) Multiplex 测量的抗尖峰 IgG 抗体的两项测定中，也观察到加强剂量后 28 天的抗体滴度高于第二次剂量后 28 天的抗体滴度。加强剂量后引起的局部和全身不良反应的频率与 mRNA-1273 的主要双剂量系列中的第二剂（50μg 或 100μg）后的频率相似；在主动提供的不良事件中没有观察到新的信号； 1个月随访期间未报告严重不良事件。这些结果表明，在完成初级两剂系列后 6 个月以上加强注射 mRNA-1273 是安全的，并且产生的 nAb 滴度在统计上显着高于初级疫苗系列后检测到的峰值滴度，这表明 mRNA-1273 加强剂量可能会提高疫苗针对 SARS-CoV-2 引起的感染和疾病的有效性。第三剂 COVID-19 疫苗 mRNA-1273 是安全的，其 SARS-CoV-2 中和抗体滴度比完成两剂系列后观察到的峰值水平几乎高出两倍，凸显了加强剂量的潜在临床益处。
Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6–8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 (NCT04405076). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.7-fold (95% confidence interval (CI): 1.5, 1.9) higher than those at 28 days after the second injection of the primary series, which met the pre-specified non-inferiority criterion (primary immunogenicity objective) and might indicate a memory B cell response. The nAb titers against the Delta variant (B.1.617.2) (exploratory objective) at 1 month after the booster were 2.1-fold (95% CI: 1.8, 2.4) higher than those at 28 days after the second injection of the primary series. The seroresponse rate (95% CI (four-fold rise from baseline)) was 100% (98.7, 100.0) at 28 days after the booster compared to 98.3% (96.0, 99.4) after the primary series. The higher antibody titers at 28 days after the booster dose compared to 28 days after the second dose in the phase 3 COVE study were also observed in two assays for anti-spike IgG antibody measured by ELISA and by Meso Scale Discovery (MSD) Multiplex. The frequency of solicited local and systemic adverse reactions after the booster dose was similar to that after the second dose in the primary two-dose series of mRNA-1273 (50 µg or 100 µg); no new signals were observed in the unsolicited adverse events; and no serious adverse events were reported in the 1-month follow-up period. These results show that a booster injection of mRNA-1273 more than 6 months after completing the primary two-dose series is safe and elicited nAb titers that were statistically significantly higher than the peak titers detected after the primary vaccination series, suggesting that a booster dose of mRNA-1273 might result in increased vaccine effectiveness against infection and disease caused by SARS-CoV-2. A third dose of the COVID-19 vaccine mRNA-1273 is safe and boosts SARS-CoV-2 neutralizing antibody titers almost two-fold higher than the peak levels observed after completion of a two-dose series, highlighting the potential clinical benefit of a booster dose.
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DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
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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
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2021-11-04
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影响因子：
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2021-12-09
期刊：
The New England journal of medicine
影响因子：
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Ali K;Berman G;Zhou H;Deng W;Faughnan V;Coronado-Voges M;Ding B;Dooley J;Girard B;Hillebrand W;Pajon R;Miller JM;Leav B;McPhee R
通讯作者：
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DOI：
10.1126/science.abm0829
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2021-12-03
期刊：
Science (New York, N.Y.)
影响因子：
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DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
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作者：
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通讯作者：
COVE Study Group