tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Cong Sun[SUP] 1 [/SUP], Zhen Zhuang[SUP] 2 [/SUP], Run-Yu Yuan[SUP] 3 [/SUP], Qingbing Zheng[SUP] 4 [/SUP], Jiang-Ping Li[SUP] 1 [/SUP], Ping-Ping Zhou[SUP] 3 [/SUP], Xin-Chun Chen[SUP] 1 [/SUP], Zhe Liu[SUP] 3 [/SUP], Xiao Zhang[SUP] 1 [/SUP], Xiao-Hui Yu[SUP] 1 [/SUP], Xiang-Wei Kong[SUP] 1 [/SUP], Qian-Ying Zhu[SUP] 1 [/SUP], Qian Zhong[SUP] 1 [/SUP], Miao Xu[SUP] 1 [/SUP], Nan-Shan Zhong[SUP] 2 [/SUP], Yi-Xin Zeng[SUP] 1 [/SUP], Guo-Kai Feng[SUP] 1 [/SUP], Changwen Ke[SUP] 3 [/SUP], Jin-Cun Zhao[SUP] 2 [/SUP], Mu-Sheng Zeng[SUP] 1 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Cong Sun[SUP] 1 [/SUP], Zhen Zhuang[SUP] 2 [/SUP], Run-Yu Yuan[SUP] 3 [/SUP], Qingbing Zheng[SUP] 4 [/SUP], Jiang-Ping Li[SUP] 1 [/SUP], Ping-Ping Zhou[SUP] 3 [/SUP], Xin-Chun Chen[SUP] 1 [/SUP], Zhe Liu[SUP] 3 [/SUP], Xiao Zhang[SUP] 1 [/SUP], Xiao-Hui Yu[SUP] 1 [/SUP], Xiang-Wei Kong[SUP] 1 [/SUP], Qian-Ying Zhu[SUP] 1 [/SUP], Qian Zhong[SUP] 1 [/SUP], Miao Xu[SUP] 1 [/SUP], Nan-Shan Zhong[SUP] 2 [/SUP], Yi-Xin Zeng[SUP] 1 [/SUP], Guo-Kai Feng[SUP] 1 [/SUP], Changwen Ke[SUP] 3 [/SUP], Jin-Cun Zhao[SUP] 2 [/SUP], Mu-Sheng Zeng[SUP] 1 [/SUP]
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.