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Engineered SARS-CoV-2 receptor binding domain improves immunogenicity in mice and elicits protective immunity in hamsters
bioRxiv - Molecular Biology Pub Date : 2021-03-04 , DOI: 10.1101/2021.03.03.433558
Neil C Dalvie 1, 2 , Sergio A Rodriguez-Aponte 2, 3 , Brittany L Hartwell 2, 4 , Lisa H Tostanoski 5 , Andrew M Biedermann 1, 2 , Laura E Crowell 1, 2 , Kawaljit Kaur 6 , Ozan Kumru 6 , Lauren Carter 7, 8 , Jingyou Yu 5 , Aiquan Chang 5, 9 , Katherine McMahan 5 , Thomas Courant 10 , Celia Lebas 10 , Ashley A Lemnios 2 , Kristen A Rodrigues 2, 4, 11 , Murillo Silva 2 , Ryan S Johnston 2 , Christopher A Naranjo 2 , Mary Kate Tracey 2 , Joseph R Brady 1, 2 , Charles A Whittaker 2 , Dongsoo Yun 2 , Swagata Kar 12 , Maciel Porto 12 , Megan Lok 12 , Hanne Andersen 12 , Mark G Lewis 12 , Kerry R Love 1, 2 , Danielle L Camp 2 , Judith Maxwell Silverman 13 , Harry Kleanthous 14 , Sangeeta B Joshi 6 , David B Volkin 6 , Patrice M Dubois 10 , Nicolas Collin 10 , Neil P King 7, 8 , Dan H Barouch 4, 5, 9, 15 , Darrell J Irvine 2, 3, 4, 16 , J Christopher Love 1, 2
Affiliation  

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing costs. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

中文翻译:

工程化的 SARS-CoV-2 受体结合域可提高小鼠的免疫原性并引发仓鼠的保护性免疫

全球遏制 COVID-19 仍然需要为低收入和中等收入国家 (LMIC) 提供可获得且负担得起的疫苗。最近批准的疫苗提供了所需的干预措施,尽管其价格可能会限制其全球获取。基于重组蛋白的亚单位疫苗适用于大批量微生物生产,每年可生产数十亿剂,最大限度地降低生产成本。这些类型的疫苗是成熟的、经过验证的干预措施,具有多个安全有效的商业实例。许多此类 SARS-CoV-2 候选疫苗依赖于包含受体结合域 (RBD) 的序列,该域通过 ACE2 介导病毒进入细胞。在这里,我们报告了 RBD 的工程化序列变体,它具有高产量可制造性、与 ACE2 的高亲和力结合,与当前疫苗中使用的武汉-Hu-1 变体相比,小鼠单次给药后的免疫原性增强。针对工程蛋白产生的抗体表现出与最近报道的两种 SARS-CoV-2 关注变体 (501Y.V1/V2) 的 RBD 的异型结合。在设计的病毒样颗粒 (VLP) 上展示工程 RBD 也减少了仓鼠在病毒攻击后的体重减轻。
更新日期:2021-03-05
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