A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy.
A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy.
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DOI：
10.1371/journal.ppat.1010248
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发表时间：
2022-03
期刊：
影响因子：
6.7
通讯作者：
Bloom JD
中科院分区：
文献类型：
--
作者：
Greaney AJ;Starr TN;Eguia RT;Loes AN;Khan K;Karim F;Cele S;Bowen JE;Logue JK;Corti D;Veesler D;Chu HY;Sigal A;Bloom JD
许多SARS-CoV-2变异体在抗体靶向的关键位点上存在突变。然而，尚不清楚这些变异体感染引起的抗体是否与早期病毒分离株引起的抗体靶向病毒刺突的相同或不同区域。在这里，我们比较了感染2020年初分离株的人类产生的多克隆抗体与关注的B.1.351变体（也称为Beta或20 H/501Y.V2）的特异性，后者包含多个关键刺突表位的突变。由2020年初病毒和B.1.351感染引起的抗体的血清中和活性主要集中在刺突受体结合结构域（RBD）上。然而，在RBD内，B.1.351引发的抗体更集中于跨越位点443至452的“3类”表位，并且这些抗体的中和受残基484处的突变的影响显著较小。我们的研究结果表明，SARS-CoV-2变异体可以引发具有不同免疫优势等级的多克隆抗体。SARS-CoV-2已经在人类中传播了大约两年，新出现的变体中的突变可以削弱先前感染或疫苗接种引起的免疫力。我们对这些新变异引起的抗体反应的理解仍然有限。对于其他病毒，如流感病毒，抗原性漂移的变体可以引发针对不同位点的抗体。在这里，我们发现这一原则也适用于SARS-CoV-2。虽然“2类”RBD抗体表位在2020年初感染SARS-CoV-2的供体血清中具有免疫显性，但感染B.1.351（Beta）变体引起的抗体更集中于“3类”表位。值得注意的是，3类表位在2020年初和B.1.351病毒之间是保守的，但在Delta变异体中发生了突变，该变异体在2021年年中在全球范围内上升至高频率。随着SARS-CoV-2继续在人类中传播，个体先前的感染和疫苗接种史可能部分决定了他们对新变异病毒突变体的易感性。
Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies. SARS-CoV-2 has circulated among humans for approximately two years, and mutations in emerging variants can erode immunity elicited by prior infection or vaccination. Our understanding of the antibody response elicited by these new variants is still limited. For other viruses, such as influenza, antigenically drifted variants can elicit antibodies that target different sites. Here, we find that this principle also applies to SARS-CoV-2. While the “class 2” RBD antibody epitope is immunodominant for sera from donors infected with SARS-CoV-2 in early 2020, antibodies elicited by infection with the B.1.351 (Beta) variant are more focused on the “class 3” epitope. Notably, the class 3 epitope is conserved between the early 2020 and B.1.351 viruses, but is mutated in the Delta variant, which rose to high frequency globally in mid-2021. As SARS-CoV-2 continues to circulate among humans, individuals’ prior infection and vaccination histories may partially determine their susceptibilities to viral mutants in new variants.
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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：
64.5
作者：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
16.6
作者：
Greaney AJ;Starr TN;Barnes CO;Weisblum Y;Schmidt F;Caskey M;Gaebler C;Cho A;Agudelo M;Finkin S;Wang Z;Poston D;Muecksch F;Hatziioannou T;Bieniasz PD;Robbiani DF;Nussenzweig MC;Bjorkman PJ;Bloom JD
通讯作者：
Bloom JD
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：
6.7
作者：
Eguia RT;Crawford KHD;Stevens-Ayers T;Kelnhofer-Millevolte L;Greninger AL;Englund JA;Boeckh MJ;Bloom JD
通讯作者：
Bloom JD