Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection

• Published in: Cell discovery Vol. 7; no. 1; p. 71
• Main Authors: Zang, Jinkai, Zhu, Yuanfei, Zhou, Yu, Gu, Chenjian, Yi, Yufang, Wang, Shuxia, Xu, Shiqi, Hu, Gaowei, Du, Shujuan, Yin, Yannan, Wang, Yalei, Yang, Yong, Zhang, Xueyang, Wang, Haikun, Yin, Feifei, Zhang, Chao, Deng, Qiang, Xie, Youhua, Huang, Zhong
• Format: Journal Article
• Language: English
• Published: London Springer Nature B.V 18.08.2021; Springer Singapore; Nature Publishing Group
• Subjects: Antibodies; Antisera; COVID-19; Dosage; Immunization; Pandemics; Proteins; Severe acute respiratory syndrome coronavirus 2; Vaccines
• ISSN: 2056-5968; 2056-5968
• DOI: 10.1038/s41421-021-00315-9

Abstract Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris ( P. pastoris ) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.