Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination.
Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination.
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DOI：
10.1126/sciimmunol.abi6950
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发表时间：
2021-04-15
影响因子：
24.8
通讯作者：
Wherry EJ
中科院分区：
文献类型：
--
作者：
Goel RR;Apostolidis SA;Painter MM;Mathew D;Pattekar A;Kuthuru O;Gouma S;Hicks P;Meng W;Rosenfeld AM;Dysinger S;Lundgreen KA;Kuri-Cervantes L;Adamski S;Hicks A;Korte S;Oldridge DA;Baxter AE;Giles JR;Weirick ME;McAllister CM;Dougherty J;Long S;D'Andrea K;Hamilton JT;Betts MR;Luning Prak ET;Bates P;Hensley SE;Greenplate AR;Wherry EJ
针对SARS-CoV-2的新型mRNA疫苗已被批准用于紧急使用。尽管它们在临床试验中有效，但mRNA疫苗诱导的免疫应答数据大多局限于血清学分析。在这里，我们在33名SARS-CoV-2 naïve和11名SARS-CoV-2康复的受试者中随时间询问抗体和抗原特异性记忆B细胞。SARS-CoV-2 naïve个体需要两种疫苗剂量才能获得最佳抗体增加，特别是针对B.1.351变体的中和滴度。mRNA疫苗也能有效启动全长刺突蛋白和刺突受体结合域（RBD）的记忆B细胞，并且在第二次接种后，在所有SARS-CoV-2幼稚受试者中都能检测到，尽管记忆B细胞的反应随着年龄的增长略有下降。在SARS-CoV-2康复个体中，第一剂疫苗后抗体和记忆B细胞反应显著增强；然而，在第二次注射后，循环抗体、中和滴度或抗原特异性记忆B细胞没有增加。首次接种疫苗后的这种强劲增强与康复个体中预先存在的记忆B细胞水平密切相关，从而确定了记忆B细胞在增强对SARS-CoV-2抗原的回忆反应中的关键作用。总之，我们的数据表明mRNA疫苗具有强大的血清学和细胞启动作用，并揭示了基于先前SARS-CoV-2暴露的不同反应，因此COVID-19恢复的受试者可能只需要一次疫苗剂量即可达到抗体和记忆B细胞反应的峰值。这些发现还强调了除血清学外定义细胞反应的效用，并可能为资源有限环境下的SARS-CoV-2疫苗分配提供信息。基于先前的SARS-CoV-2暴露，确定了抗体和记忆B细胞对mRNA疫苗应答的关键差异。
Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting. Key differences in both antibody and memory B cell responses to mRNA vaccination were identified based on prior SARS-CoV-2 exposure.
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DOI：
10.1038/nrd.2017.243
发表时间：
2018-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Pardi N;Hogan MJ;Porter FW;Weissman D
通讯作者：
Weissman D
影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
DOI：
10.1038/s41577-021-00522-1
发表时间：
2021-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Carvalho T;Krammer F;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
8.7
作者：
Baumgarth N
通讯作者：
Baumgarth N
影响因子：
24.8
作者：
Kuri-Cervantes, Leticia;Pampena, Maria Betina;Betts, Michael R.
通讯作者：
Betts, Michael R.