Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2.
Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2.
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DOI：
10.1016/j.cell.2020.10.043
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发表时间：
2020-11-25
期刊：
影响因子：
64.5
通讯作者：
King NP
中科院分区：
文献类型：
--
作者：
Walls AC;Fiala B;Schäfer A;Wrenn S;Pham MN;Murphy M;Tse LV;Shehata L;O'Connor MA;Chen C;Navarro MJ;Miranda MC;Pettie D;Ravichandran R;Kraft JC;Ogohara C;Palser A;Chalk S;Lee EC;Guerriero K;Kepl E;Chow CM;Sydeman C;Hodge EA;Brown B;Fuller JT;Dinnon KH 3rd;Gralinski LE;Leist SR;Gully KL;Lewis TB;Guttman M;Chu HY;Lee KK;Fuller DH;Baric RS;Kellam P;Carter L;Pepper M;Sheahan TP;Veesler D;King NP
需要一种安全、有效且可扩展的疫苗来阻止正在进行的 SARS-CoV-2 大流行。我们描述了基于结构的自组装蛋白纳米颗粒免疫原的设计，该免疫原可在小鼠体内引发针对 SARS-CoV-2 的有效且保护性的抗体反应。纳米颗粒疫苗在高免疫原性阵列中显示 60 个 SARS-CoV-2 刺突受体结合域 (RBD)，尽管剂量低 5 倍，但诱导的中和抗体滴度比灌注前稳定的刺突高 10 倍。 RBD纳米粒子引发的抗体针对多个不同的表位，表明它们可能不容易受到逃逸突变的影响，并且表现出比恢复期人类血清更低的结合：中和比，这可以最大限度地降低疫苗相关的增强性呼吸道疾病的风险。组装纳米颗粒的高产率和稳定性表明纳米颗粒疫苗的生产将具有高度可扩展性。这些结果凸显了强大的抗原展示平台的实用性，并启动了 cGMP 生产工作，以将 SARS-CoV-2-RBD 纳米颗粒疫苗推向临床。双组分纳米颗粒平台能够快速生成 SARS-CoV-2 疫苗 RBD 纳米颗粒疫苗可引发有效的中和抗体反应 纳米颗粒疫苗引发的抗体靶向多个非重叠表位 主要纳米颗粒候选疫苗正在生产用于临床试验 Walls 等人。描述了一种潜在的 COVID-19 纳米颗粒疫苗，该疫苗由自组装蛋白纳米颗粒制成，在高度免疫原性阵列中显示 SARS-CoV-2 受体结合域，让人想起天然病毒。他们的纳米颗粒候选疫苗可引发多样化、有效的保护性抗体反应，其中中和抗体滴度比融合前稳定的刺突胞外域三聚体高 10 倍。
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic. Two-component nanoparticle platform enabled rapid generation of SARS-CoV-2 vaccines The RBD-nanoparticle vaccines elicit potent neutralizing antibody responses Nanoparticle vaccine-elicited antibodies target multiple non-overlapping epitopes The lead nanoparticle vaccine candidate is being manufactured for clinical trials Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer.
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DOI：
10.4049/jimmunol.2000583
发表时间：
2020-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Alsoussi WB;Turner JS;Case JB;Zhao H;Schmitz AJ;Zhou JQ;Chen RE;Lei T;Rizk AA;McIntire KM;Winkler ES;Fox JM;Kafai NM;Thackray LB;Hassan AO;Amanat F;Krammer F;Watson CT;Kleinstein SH;Fremont DH;Diamond MS;Ellebedy AH
通讯作者：
Ellebedy AH
影响因子：
7
作者：
Irvine DJ;Read BJ
通讯作者：
Read BJ
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
17.1
作者：
Bruun TUJ;Andersson AC;Draper SJ;Howarth M
通讯作者：
Howarth M
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.