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.
【저자키워드】 SARS-CoV-2, Vaccine, Receptor binding domain, Nanoparticles, SpyTag-SpyCatcher, covalent conjugation, 【초록키워드】 COVID-19, coronavirus disease, ACE2, Vaccine, Vaccine development, pandemic, SARS-CoV-2 coronavirus, in vitro, virus, angiotensin-converting enzyme 2, immunization, Neutralizing activity, Health, pseudovirus, mice, RBD, sera, vaccine candidate, adjuvant, membrane fusion, receptor, platform, Antisera, binding, Receptor binding, domain, vaccine candidates, sigma, MOST, System, effective, immunized, highlight, flexible, greater, produced, resulting, blocked, caused, exhibited, the spike protein, adopted, the RBD, the vaccine, monomeric RBD, the SARS-CoV-2, 【제목키워드】 spike, nanoparticle, Rapid, development, candidate,