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Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2
Yu Liang; Jing Zhang; Run Yu Yuan; Mei Yu Wang; Peng He; Ji Guo Su; Zi Bo Han; Yu Qin Jin; Jun Wei Hou; Hao Zhang; Xue Feng Zhang; Shuai Shao; Ya Nan Hou; Zhao Ming Liu; Li Fang Du; Fu Jie Shen; Wei Min Zhou; Fang Tang; Ze Hua Lei; Shuo Liu; Wei Zhen; Jin Juan Wu; Xiang Zheng; Ning Liu; Shi Chen; Zhi Jing Ma; Fan Zheng; Si Yu Ren; Zhong Yu Hu; Gui Zhen Wu; Wei Jin Huang; Chang Wen Ke; Qi Ming Li.
  • Yu Liang; National Vaccine and Serum Institute
  • Jing Zhang; National Vaccine and Serum Institute
  • Run Yu Yuan; Guangdong Provincial Institute of Public Health
  • Mei Yu Wang; National Institute for Food and Drug Control
  • Peng He; National Institute for Food and Drug Control
  • Ji Guo Su; National Vaccine and Serum Institute
  • Zi Bo Han; National Vaccine and Serum Institute
  • Yu Qin Jin; National Vaccine and Serum Institute
  • Jun Wei Hou; National Vaccine and Serum Institute
  • Hao Zhang; National Vaccine and Serum Institute
  • Xue Feng Zhang; National Vaccine and Serum Institute
  • Shuai Shao; National Vaccine and Serum Institute
  • Ya Nan Hou; National Vaccine and Serum Institute
  • Zhao Ming Liu; National Vaccine and Serum Institute
  • Li Fang Du; National Vaccine and Serum Institute
  • Fu Jie Shen; National Vaccine and Serum Institute
  • Wei Min Zhou; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC)
  • Fang Tang; National Vaccine and Serum Institute
  • Ze Hua Lei; National Vaccine and Serum Institute
  • Shuo Liu; National Institute for Food and Drug Control
  • Wei Zhen; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC)
  • Jin Juan Wu; National Vaccine and Serum Institute
  • Xiang Zheng; National Vaccine and Serum Institute
  • Ning Liu; National Vaccine and Serum Institute
  • Shi Chen; National Vaccine and Serum Institute
  • Zhi Jing Ma; National Vaccine and Serum Institute
  • Fan Zheng; National Vaccine and Serum Institute
  • Si Yu Ren; National Vaccine and Serum Institute
  • Zhong Yu Hu; National Vaccine and Serum Institute
  • Gui Zhen Wu; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC)
  • Wei Jin Huang; National Institute for Food and Drug Control
  • Chang Wen Ke; Guangdong Provincial Institute of Public Health
  • Qi Ming Li; National Vaccine and Serum Institute
Preprint in English | bioRxiv | ID: ppbiorxiv-448958
ABSTRACT
The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Randomized controlled trials Topics: Vaccines / Variants Language: English Year: 2021 Document Type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Randomized controlled trials Topics: Vaccines / Variants Language: English Year: 2021 Document Type: Preprint