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SARS-CoV-2蛋白纳米颗粒疫苗可激发有效的中和抗体反应
作者:小柯机器人 发布时间:2020/11/4 16:30:59

美国华盛顿大学Neil P. King、David Veesler等研究人员合作发现,SARS-CoV-2蛋白纳米颗粒疫苗可激发有效的中和抗体反应。2020年10月30日,《细胞》杂志在线发表了这项成果。

研究人员报道了基于结构的自组装蛋白纳米颗粒免疫原,其在小鼠中引发针对SARS-CoV-2的有效和保护性抗体反应。纳米粒子疫苗在高度免疫原性的阵列中显示了60个SARS-CoV-2刺突受体结合域(RBD);尽管剂量降低了五倍,但诱导的中和抗体滴度却比融合前稳定的刺突高了十倍。RBD纳米颗粒引发的抗体靶向了多个不同的表位,表明它们可能不容易逃脱突变,并且与恢复期的人血清相比具有较低的结合:中和率,这可以使与疫苗相关的增强呼吸道疾病的风险最小化。组装后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的可量产性。

这些结果凸显了强大抗原展示平台的实用性,并启动了cGMP制造来将SARS-CoV-2-RBD纳米颗粒疫苗推进临床。

研究人员表示,目前需要一种安全、有效且可大量生产的疫苗来阻止SARS-CoV-2的大流行。

附:英文原文

Title: Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2

Author: Alexandra C. Walls, Brooke Fiala, Alexandra Schfer, Samuel Wrenn, Minh N. Pham, Michael Murphy, Longping V. Tse, Laila Shehata, Megan A. OConnor, Chengbo Chen, Mary Jane Navarro, Marcos C. Miranda, Deleah Pettie, Rashmi Ravichandran, John C. Kraft, Cassandra Ogohara, Anne Palser, Sara Chalk, E-Chiang Lee, Kathryn Guerriero, Elizabeth Kepl, Cameron M. Chow, Claire Sydeman, Edgar A. Hodge, Brieann Brown, Jim T. Fuller, Kenneth H. Dinnon, Lisa E. Gralinski, Sarah R. Leist, Kendra L. Gully, Thomas B. Lewis, Miklos Guttman, Helen Y. Chu, Kelly K. Lee, Deborah H. Fuller, Ralph S. Baric, Paul Kellam, Lauren Carter, Marion Pepper, Timothy P. Sheahan, David Veesler, Neil P. King

Issue&Volume: 2020-10-30

Abstract: 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 ten-fold higher than the prefusion-stabilized spike despite a five-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.

DOI: 10.1016/j.cell.2020.10.043

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31450-1

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/