Dalvie Neil C, Rodriguez-Aponte Sergio A, Hartwell Brittany L, Tostanoski Lisa H, Biedermann Andrew M, Crowell Laura E, Kaur Kawaljit, Kumru Ozan S, Carter Lauren, Yu Jingyou, Chang Aiquan, McMahan Katherine, Courant Thomas, Lebas Celia, Lemnios Ashley A, Rodrigues Kristen A, Silva Murillo, Johnston Ryan S, Naranjo Christopher A, Tracey Mary Kate, Brady Joseph R, Whittaker Charles A, Yun Dongsoo, Brunette Natalie, Wang Jing Yang, Walkey Carl, Fiala Brooke, Kar Swagata, Porto Maciel, Lok Megan, Andersen Hanne, Lewis Mark G, Love Kerry R, Camp Danielle L, Silverman Judith Maxwell, Kleanthous Harry, Joshi Sangeeta B, Volkin David B, Dubois Patrice M, Collin Nicolas, King Neil P, Barouch Dan H, Irvine Darrell J, Love J Christopher
Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2021 Sep 21;118(38). doi: 10.1073/pnas.2106845118.
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 cost. 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.
全球新冠疫情防控仍需要为低收入和中等收入国家（LMICs）提供可及且价格合理的疫苗。近期获批的疫苗虽提供了必要的干预措施，但价格可能限制其全球可及性。基于重组蛋白的亚单位疫苗适合大规模微生物生产，每年可生产数十亿剂，从而将生产成本降至最低。这类疫苗是成熟的、经过验证的干预措施，有多个安全有效的商业实例。许多针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的此类候选疫苗依赖于包含受体结合域（RBD）的序列，该结构域通过血管紧张素转化酶2（ACE2）介导病毒进入细胞。在此，我们报告了一种RBD的工程序列变体，与当前疫苗中使用的武汉-1变体相比，该变体在小鼠中单次给药后表现出高产率的可制造性、与ACE2的高亲和力结合以及增强的免疫原性。针对该工程蛋白产生的抗体对两种最近报告的值得关注的SARS-CoV-2变体（501Y.V1/V2）的RBD表现出异型结合。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。
