德国BioNTech公司
研究人员报道了两个BNT162b候选疫苗的临床前开发，其中包含脂质纳米颗粒（LNP）包裹的编码SARS-CoV-2突刺糖蛋白衍生免疫原的核苷修饰mRNA。 BNT162b1编码一个可溶的、分泌的、三聚的受体结合域（RBD-foldon）。BNT162b2编码全长跨膜突刺糖蛋白，并锁定在其融合前构象（P2 S）中。RBD-foldon的柔性束缚RBD以高亲和力结合ACE2。大约20％的P 2S三聚体处于两个RBD“向下”，一个RBD“向上”状态。
在小鼠中，任一候选者的肌肉注射剂量均可引起剂量依赖性抗体反应，并具有较高的病毒抑制滴度和强TH1 CD4+和IFNγ+ CD8+ T细胞反应。用BNT162b候选物对恒河猴进行初次/加强免疫接种可引起SARS-CoV-2中和抗体，其平均滴度为SARS-CoV-2恢复期人血清的8.2至18.2倍。候选疫苗可保护猕猴免受SARS-CoV-2感染，而BNT162b2可保护下呼吸道免受病毒RNA的侵害，且无疾病增强的迹象。
在德国和美国进行的第一阶段试验均对这两种候选疫苗进行了评估。BNT162b2正处于一项关键的全球2/3期临床试验（NCT04380701、NCT04368728）评估中。
研究人员表示，目前迫切需要一种安全有效的COVID-19疫苗来免疫大量人群。
附：英文原文
Title: Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2
Author: Annette B. Vogel, Isis Kanevsky, Ye Che, Kena A. Swanson, Alexander Muik, Mathias Vormehr, Lena M. Kranz, Kerstin C. Walzer, Stephanie Hein, Alptekin Gler, Jakob Loschko, Mohan S. Maddur, Ayuko Ota-Setlik, Kristin Tompkins, Journey Cole, Bonny G. Lui, Thomas Ziegenhals, Arianne Plaschke, David Eisel, Sarah C. Dany, Stephanie Fesser, Stephanie Erbar, Ferdia Bates, Diana Schneider, Bernadette Jesionek, Bianca Snger, Ann-Kathrin Wallisch, Yvonne Feuchter, Hanna Junginger, Stefanie A. Krumm, Andr P. Heinen, Petra Adams-Quack, Julia Schlereth, Stefan Schille, Christoph Krner, Ramn de la Caridad Gimil Garcia, Thomas Hiller, Leyla Fischer, Rani S. Sellers, Shambhunath Choudhary, Olga Gonzalez, Fulvia Vascotto, Matthew R. Gutman, Jane A. Fontenot, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, Seungil Han, Andreas A. H. Su, Joshua A. Lees, Nicole L. Nedoma, Ellene H. Mashalidis, Parag V. Sahasrabudhe, Charles Y. Tan, Danka Pavliakova, Guy Singh, Camila Fontes-Garfias, Michael Pride, Ingrid L. Scully, Tara Ciolino, Jennifer Obregon, Michal Gazi, Ricardo Carrion, Kendra J. Alfson, Warren V. Kalina, Deepak Kaushal, Pei-Yong Shi, Thorsten Klamp, Corinna Rosenbaum, Andreas N. Kuhn, zlem Treci, Philip R. Dormitzer, Kathrin U. Jansen, Ugur Sahin
Issue&Volume: 2021-02-01
Abstract: A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD ‘down,’ one-RBD ‘up’ state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFNγ+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States1–3. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).
DOI: 10.1038/s41586-021-03275-y
Source: https://www.nature.com/articles/s41586-021-03275-y
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
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