Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations.
Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations.
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DOI：
10.1016/j.immuni.2021.07.008
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发表时间：
2021-08-10
期刊：
影响因子：
32.4
通讯作者：
Bieniasz PD
中科院分区：
文献类型：
--
作者：
Muecksch F;Weisblum Y;Barnes CO;Schmidt F;Schaefer-Babajew D;Wang Z;C Lorenzi JC;Flyak AI;DeLaitsch AT;Huey-Tubman KE;Hou S;Schiffer CA;Gaebler C;Da Silva J;Poston D;Finkin S;Cho A;Cipolla M;Oliveira TY;Millard KG;Ramos V;Gazumyan A;Rutkowska M;Caskey M;Nussenzweig MC;Bjorkman PJ;Hatziioannou T;Bieniasz PD
感染引起的抗体会在生发中心积累体细胞突变，从而增加对同源抗原的亲和力。我们分析了 6 组独立的克隆相关严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 尖峰受体结合域 (RBD) 特异性抗体，这些抗体来自 5 名感染后不久和恢复期的个体，以确定数月内成熟的影响。除了增加亲和力和中和效力之外，抗体进化还改变了获得病毒抗性和限制中和逃逸选择的突变途径。对于某些抗体来说，成熟需要多次替换才能逃脱。对于某些抗体，亲和力成熟能够中和所关注的循环 SARS-CoV-2 变体和异源 sarbeco 病毒。抗体-抗原结构揭示了这些特性是由取代引起的，这些取代使得与 RBD 的界面存在额外的可变性。这些发现表明，通过长期或重复的抗原暴露来增加抗体多样性可能会提高对多样化 SARS-CoV-2 群体的保护，或许还可以预防其他大流行威胁冠状病毒。 SARS-CoV-2 RBD 结合抗体在数月的恢复期中积累突变，但成熟如何影响抗体特性尚不清楚。 Muecksch 等人。分析来自恢复期供体的 6 组克隆相关中和抗体，揭示抗体成熟会增加亲和力、效力和广度，并限制病毒逃逸选择。他们还确定了成熟过程中这些改进的抗体特性的结构基础。
Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options. For some antibodies, maturation imposed a requirement for multiple substitutions to enable escape. For certain antibodies, affinity maturation enabled the neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses. SARS-CoV-2 RBD-binding antibodies accumulate mutations over months of convalescence, but how maturation affects antibody properties is unclear. Muecksch et al. analyze 6 groups of clonally related neutralizing antibodies from convalescent donors and reveal that antibody maturation increases affinity, potency, and breadth, and restricts viral escape options. They also identify the structural basis for these improved antibody properties during maturation.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
14.9
作者：
Abascal F;Zardoya R;Telford MJ
通讯作者：
Telford MJ
影响因子：
15.3
作者：
Gaebler, Christian;Lorenzi, Julio C. C.;Nussenzweig, Michel C.
通讯作者：
Nussenzweig, Michel C.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH