Early human B cell signatures of the primary antibody response to mRNA vaccination.
Early human B cell signatures of the primary antibody response to mRNA vaccination.
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对mRNA疫苗接种的初级抗体应答的早期人B细胞特征。
DOI：
10.1073/pnas.2204607119
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发表时间：
2022-07-12
影响因子：
11.1
通讯作者：
Moir, Susan
中科院分区：
文献类型：
--
作者：
Kardava, Lela;Rachmaninoff, Nicholas;Lau, William W.;Buckner, Clarisa M.;Trihemasava, Krittin;Blazkova, Jana;de Assis, Felipe Lopes;Wang, Wei;Zhang, Xiaozhen;Wang, Yimeng;Chiang, Chi-, I;Narpala, Sandeep;McCormack, Genevieve E.;Liu, Can;Seamon, Catherine A.;Sneller, Michael C.;O'Connell, Sarah;Li, Yuxing;McDermott, Adrian B.;Chun, Tae-Wook;Fauci, Anthony S.;Tsang, John S.;Moir, Susan
由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的大流行加速了信使RNA（mRNA）疫苗的开发，该疫苗已被证明对COVID-19非常有效。然而，抗体反应变化很大，并随着时间的推移而减弱。本研究评价了一抗对基于SARS-CoV-2 mRNA的疫苗接种的反应范围和动力学，并与参与产生和维持这种反应的B细胞平行。这些细胞包括浆母细胞，即免疫后迅速但短暂产生的抗体分泌细胞，以及记忆B细胞，即可以提供持久免疫力的异质群体。我们的研究结果表明，抗体反应与早期浆母细胞密切相关，而细胞反应是由一个独特的记忆B细胞群体维持的。针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的信使RNA（mRNA）疫苗在诱导保护性免疫方面是高度有效的。然而，在某些个体中观察到较弱的抗体反应，并且免疫的细胞相关性仍然定义不清，尤其是对于B细胞。在这里，我们使用无偏的方法纵向解剖一抗，浆母细胞和记忆B细胞（MBC）的反应，两个剂量的mRNA-1273疫苗在SARS-CoV-2的幼稚成人。协调免疫球蛋白A（伊加）和IgG抗体反应之前，在两个剂量后，但更早和更强烈的剂量2后，突发的尖峰特异性浆母细胞。虽然抗体和B细胞应答通常是稳健的，但它们在队列内也有变化，并且在剂量-2峰值后随时间推移而降低。第1剂后的抗原非特异性接种后浆母细胞频率和第2剂后早期的加标特异性对应物均与随后的抗体水平相关。早期浆母细胞和抗体之间的这种相关性在接种后6个月测量的滴度中仍然存在。几个不同的抗原特异性MBC人群出现接种后不同的动力学，包括两个MBC人群与2个月和6个月的抗体滴度。两者均为IgG表达MBC：一个不太成熟，在第一次给药后作为相关物出现，而另一个MBC相关物显示出更成熟和静止的表型，在第2次给药后作为相关物出现。后者MBC也是第6个月观察到的持续加标特异性MBC反应的主要贡献因素。因此，在第一和第二剂量后以不同动力学出现的这些浆母细胞和MBC是响应于基于mRNA的疫苗接种的抗体的大小和持久性的潜在决定因素。
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accelerated development of messenger RNA (mRNA) vaccines, which have proven to be highly effective against COVID-19. However, antibody responses vary widely and wane over time. This study evaluated the range and kinetics of the primary antibody response to SARS-CoV-2 mRNA-based vaccination in parallel with the B cells that are involved in generating and maintaining this response. These include plasmablasts, the antibody-secreting cells that arise rapidly yet transiently following immunization, and memory B cells, a heterogeneous population that can provide long-lasting immunity. Our results show that the antibody response was tightly linked to early plasmablasts, while the cellular response was sustained by a distinct population of memory B cells. Messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective at inducing protective immunity. However, weak antibody responses are seen in some individuals, and cellular correlates of immunity remain poorly defined, especially for B cells. Here we used unbiased approaches to longitudinally dissect primary antibody, plasmablast, and memory B cell (MBC) responses to the two-dose mRNA-1273 vaccine in SARS-CoV-2–naive adults. Coordinated immunoglobulin A (IgA) and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses but earlier and more intensely after dose 2. While antibody and B cell cellular responses were generally robust, they also varied within the cohort and decreased over time after a dose-2 peak. Both antigen-nonspecific postvaccination plasmablast frequency after dose 1 and their spike-specific counterparts early after dose 2 correlated with subsequent antibody levels. This correlation between early plasmablasts and antibodies remained for titers measured at 6 months after vaccination. Several distinct antigen-specific MBC populations emerged postvaccination with varying kinetics, including two MBC populations that correlated with 2- and 6-month antibody titers. Both were IgG-expressing MBCs: one less mature, appearing as a correlate after the first dose, while the other MBC correlate showed a more mature and resting phenotype, emerging as a correlate later after dose 2. This latter MBC was also a major contributor to the sustained spike-specific MBC response observed at month 6. Thus, these plasmablasts and MBCs that emerged after both the first and second doses with distinct kinetics are potential determinants of the magnitude and durability of antibodies in response to mRNA-based vaccination.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
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
影响因子：
24.8
作者：
Kuri-Cervantes, Leticia;Pampena, Maria Betina;Betts, Michael R.
通讯作者：
Betts, Michael R.
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
影响因子：
24.8
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
通讯作者：
Wherry EJ