Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.
Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.
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DOI：
10.1038/s41467-023-44265-0
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发表时间：
2024-01-03
影响因子：
16.6
通讯作者：
Joyce, M. Gordon
中科院分区：
文献类型：
--
作者：
Sankhala, Rajeshwer S.;Lal, Kerri G.;Jensen, Jaime L.;Dussupt, Vincent;Mendez-Rivera, Letzibeth;Bai, Hongjun;Wieczorek, Lindsay;Mayer, Sandra V.;Zemil, Michelle;Wagner, Danielle A.;Townsley, Samantha M.;Hajduczki, Agnes;Chang, William C.;Chen, Wei-Hung;Donofrio, Gina C.;Jian, Ningbo;King, Hannah A. D.;Lorang, Cynthia G.;Martinez, Elizabeth J.;Rees, Phyllis A.;Peterson, Caroline E.;Schmidt, Fabian;Hart, Tricia J.;Duso, Debra K.;Kummer, Lawrence W.;Casey, Sean P.;Williams, Jazmean K.;Kannan, Shruthi;Slike, Bonnie M.;Smith, Lauren;Swafford, Isabella;Thomas, Paul V.;Tran, Ursula;Currier, Jeffrey R.;Bolton, Diane L.;Davidson, Edgar;Doranz, Benjamin J.;Hatziioannou, Theodora;Bieniasz, Paul D.;Paquin-Proulx, Dominic;Reiley, William W.;Rolland, Morgane;Sullivan, Nancy J.;Vasan, Sandhya;Collins, Natalie D.;Modjarrad, Kayvon;Gromowski, Gregory D.;Polonis, Victoria R.;Michael, Nelson L.;Krebs, Shelly J.;Joyce, M. Gordon
SARS-CoV-2引起关注的变种(VOC)的反复出现，降低了对疫苗引发抗体的敏感性，突显了开发具有广泛保护作用的下一代候选疫苗的必要性。在这里，我们描述了SARS-CoV-2Spike Ferritin纳米颗粒(SpFN)疫苗候选疫苗与包括QS21(ALFQ)在内的陆军脂质体制剂在非人类灵长类动物中诱导的抗体反应。通过分离和鉴定几种针对Spike受体结合域(RBD)、N末端结构域(NTD)或S2结构域的单抗，我们定义了SpFN诱导的疫苗诱导的交叉反应性单抗(MAbs)的分子识别。我们确定了六种具有广泛的肉瘤病毒交叉反应的中和抗体，它们概括了血清多克隆抗体的反应。特别是，RBD单抗WRAIR-5001与保守的隐匿区结合，与肉瘤病毒分支1和2具有高亲和力，包括Omicron变种，而在小鼠攻击研究中，RBD单抗WRAIR-5021提供了对B.1.617.2(Delta)的完全保护。我们的数据进一步强调了SpFN疫苗能够刺激针对刺突保守区域的交叉反应B细胞，具有对抗SARS CoV-1和SARS-CoV-2变种的活性。一种佐剂SARS-CoV-2刺状铁蛋白纳米粒疫苗可以在非人类灵长类动物中诱导出具有相对广泛的肉瘤病毒活性的抗体。在这里，作者分离并在结构上表征了几种单抗，提供了对靶标表位和广泛反应性的见解。
The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants. An adjuvanted SARS-CoV-2 spike-ferritin nanoparticle vaccine can elicit antibodies with relatively broad sarbecovirus activity in non-human primates. Here, the authors isolate and structurally characterize several monoclonal antibodies providing insights into the targeted epitopes and broad reactivity.
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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
广义X射线和中子晶体学分析：更准确、更完整的生物大分子结构。
DOI：
10.1107/s0907444909011548
发表时间：
2009-06
影响因子：
2.2
作者：
Adams, Paul D.;Mustyakimov, Marat;Afonine, Pavel V.;Langan, Paul
通讯作者：
Langan, Paul
影响因子：
7.7
作者：
Fielding, Ceri Alan;Sabberwal, Pragati;Williamson, James C.;Greenwood, Edward J. D.;Crozier, Thomas W. M.;Zelek, Wioleta;Seow, Jeffrey;Graham, Carl;Huettner, Isabella;Edgeworth, Jonathan D.;Price, David A.;Morgan, Paul B.;Ladell, Kristin;Eberl, Matthias;Humphreys, Ian R.;Merrick, Blair;Doores, Katie;Wilson, Sam J.;Lehner, Paul J.;Wang, Eddie C. Y.;Stanton, Richard J.
通讯作者：
Stanton, Richard J.
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
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K