Broad and potent neutralizing antibodies are elicited in vaccinated individuals following Delta/BA.1 breakthrough infection.
Broad and potent neutralizing antibodies are elicited in vaccinated individuals following Delta/BA.1 breakthrough infection.
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作者：
尽管新冠肺炎疫苗在预防感染和/或严重疾病方面取得了成功，但由于疫苗衍生免疫力的减弱以及编码SPEKE逃逸突变的新变种的出现，接种疫苗的个人中感染SARS-CoV-2的人数有所增加。在接种疫苗的个体中发生突破性感染后，在血清/血浆中观察到中和广度增加。然而，暴露于异源尖峰如何在单抗(MAb)水平上扩大中和反应尚不完全清楚。通过从三个在感染Delta或OMICRON/BA1之前接受两剂BNT162b2疫苗的人分离出119株单抗，我们发现血清广度是由于存在具有广泛中和活性的体细胞突变单抗，表明先前新冠肺炎疫苗接种后产生的B细胞重新激活和成熟。分离的单抗经常显示当前循环中的变异体包括BA.2.75.2、XBB、XBB.1.5和BQ.1.1的中和性降低，证实了对Spike进化和逃避中和的持续选择性压力。然而，对所有变异体表现出有效交叉中和的mAbs的分离表明，在受体结合域上存在保守的表位，在较小程度上存在N端结构域。这些发现对下一代新冠肺炎疫苗的尖峰抗原的选择有一定的指导意义。随着SARS-CoV-2病毒变种的出现，接种疫苗的个人感染人数有所增加。在这里，我们从经历突破性感染的个人(Delta或BA.1)中分离出单抗(MAbs)，以确定暴露于异源尖峰是如何在单克隆水平上扩大中和抗体反应的。所有分离的单抗均对疫苗的尖峰蛋白和感染变异体具有反应性。虽然许多单抗对当前循环中的变异体显示出较低的中和性，但我们发现具有广泛和有效的BA.2.75.2、XBB、XBB.1.5和BQ.1.1中和性的单抗，表明在Spike上存在保守的表位。这些结果表明，基于变种的疫苗增强剂具有扩大疫苗反应的潜力。
Despite the success of COVID-19 vaccines in preventing infection and/or severe disease, there has been an increase in SARS-CoV-2 infections in vaccinated individuals owing to the waning vaccine-derived immunity, and the emergence of new variants which encode escape mutations in Spike. Following breakthrough infection in vaccinated individuals, an increase in neutralization breadth has been observed in sera/plasma. However, how exposure to a heterologous Spike broadens the neutralizing response at the monoclonal antibody (mAb) level is not fully understood. Through isolation of 119 mAbs from three individuals receiving two doses of BNT162b2 vaccine before becoming Delta or Omicron/BA.1 infected, we show that serum breadth occurs due to the presence of somatically mutated mAbs with broad neutralization activity indicative of re-activation and maturation of B cells generated through previous COVID-19 vaccination. Isolated mAbs frequently show reduced neutralization of current circulating variants including BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 confirming continuous selective pressure on Spike to evolve and evade neutralization. However, isolation of mAbs that display effective cross-neutralization against all variants indicates the presence of conserved epitopes on the receptor binding domain and a lesser extent the N-terminal domain. These findings have implications for the selection of Spike antigens for next-generation COVID-19 vaccines. With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level. All mAbs isolated had reactivity to the Spike of the vaccine and infection variant. While many mAbs showed reduced neutralization of current circulating variants, we identified mAbs with broad and potent neutralization of BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 indicating the presence of conserved epitopes on Spike. These results indicate that variant-based vaccine boosters have the potential to broaden the vaccine response.
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影响因子：
64.8
作者：
Alsoussi, Wafaa B.;Malladi, Sameer Kumar;Ellebedy, Ali H.
通讯作者：
Ellebedy, Ali H.
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：
64.8
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：
10.1056/nejmoa2119451
发表时间：
2022-04-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Andrews N;Stowe J;Kirsebom F;Toffa S;Rickeard T;Gallagher E;Gower C;Kall M;Groves N;O'Connell AM;Simons D;Blomquist PB;Zaidi A;Nash S;Iwani Binti Abdul Aziz N;Thelwall S;Dabrera G;Myers R;Amirthalingam G;Gharbia S;Barrett JC;Elson R;Ladhani SN;Ferguson N;Zambon M;Campbell CNJ;Brown K;Hopkins S;Chand M;Ramsay M;Lopez Bernal J
通讯作者：
Lopez Bernal J
影响因子：
9.4
作者：
Addetia A;Crawford KHD;Dingens A;Zhu H;Roychoudhury P;Huang ML;Jerome KR;Bloom JD;Greninger AL
通讯作者：
Greninger AL