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Development of Receptor Binding Domain (RBD)-Conjugated Nanoparticle Vaccines with Broad Neutralization against SARS-CoV-2 Delta and Other Variants.

Abstract
The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants.
AuthorsRan Chen, Xiantao Zhang, Yaochang Yuan, Xiaohui Deng, Bolin Wu, Zhihui Xi, Guanwen Wang, Yingtong Lin, Rong Li, Xuemei Wang, Fan Zou, Liting Liang, Haiping Yan, Chaofeng Liang, Yuzhuang Li, Shijian Wu, Jieyi Deng, Mo Zhou, Xu Zhang, Congrong Li, Xiuqing Bu, Yi Peng, Changwen Ke, Kai Deng, Xin He, Yiwen Zhang, Zhenhai Zhang, Ting Pan, Hui Zhang
JournalAdvanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 9 Issue 11 Pg. e2105378 (04 2022) ISSN: 2198-3844 [Electronic] Germany
PMID35142444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
Chemical References
  • Broadly Neutralizing Antibodies
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Conjugate
  • spike protein, SARS-CoV-2
Topics
  • Animals
  • Broadly Neutralizing Antibodies
  • COVID-19 (prevention & control)
  • Macaca mulatta (metabolism)
  • Mice
  • Nanoparticles
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Conjugate

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