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ACS Nano
. 2021 Jan 19.
doi: 10.1021/acsnano.0c08379. Online ahead of print.
Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates
Yin-Feng Kang 1 , Cong Sun 1 , Zhen Zhuang 2 , Run-Yu Yuan 3 , Qingbing Zheng 4 , Jiang-Ping Li 1 , Ping-Ping Zhou 3 , Xin-Chun Chen 1 , Zhe Liu 3 , Xiao Zhang 1 , Xiao-Hui Yu 1 , Xiang-Wei Kong 1 , Qian-Ying Zhu 1 , Qian Zhong 1 , Miao Xu 1 , Nan-Shan Zhong 2 , Yi-Xin Zeng 1 , Guo-Kai Feng 1 , Changwen Ke 3 , Jin-Cun Zhao 2 , Mu-Sheng Zeng 1
Affiliations
- PMID: 33464829
- DOI: 10.1021/acsnano.0c08379
Abstract
The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticle vaccine candidates, namely, RBD-Ferritin (24-mer), RBD-mi3 (60-mer), and RBD-I53-50 (120-mer), via covalent conjugation using the SpyTag-SpyCatcher system. When mice were immunized with the RBD-conjugated nanoparticles (NPs) in conjunction with the AddaVax or Sigma Adjuvant System, the resulting antisera exhibited 8- to 120-fold greater neutralizing activity against both a pseudovirus and the authentic virus than those of mice immunized with monomeric RBD. Most importantly, sera from mice immunized with RBD-conjugated NPs more efficiently blocked the binding of RBD to ACE2 in vitro, further corroborating the promising immunization effect. Additionally, the vaccine has distinct advantages in terms of a relatively simple scale-up and flexible assembly. These results illustrate that the SARS-CoV-2 RBD-conjugated nanoparticles developed in this study are a competitive vaccine candidate and that the carrier nanoparticles could be adopted as a universal platform for a future vaccine development.
Keywords: SARS-CoV-2; SpyTag-SpyCatcher; covalent conjugation; nanoparticles; receptor binding domain; vaccine.